Biol. Rev. (2006), 81, pp. 425–455.

f 2006 Cambridge Philosophical Society 425

doi:10.1017/S1464793106007068 Printed in the United Kingdom
First published online 22 June 2006

Human cell type diversity, evolution,

development, and classification with special
reference to cells derived from the neural crest
Matthew K. Vickaryous* and Brian K. Hall
Department of Biology, Life Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4J1

(Received 6 July 2005 ; revised 29 March 2006; accepted 3 April 2006)

ABSTRACT

Metazoans are composed of a finite number of recognisable cell types. Similar to the relationship between species
and ecosystems, knowledge of cell type diversity contributes to studies of complexity and evolution. However,
as with other units of evolution, the cell type often resists definition. This review proposes guidelines for charac-
terising cell types and discusses cell homology and the various developmental pathways by which cell types arise,
including germ layers, blastemata (secondary development/neurulation), stem cells, and transdifferentiation. An
updated list of cell types is presented for a familiar, albeit overlooked model taxon, adult Homo sapiens, with 411
cell types, including 145 types of neurons, recognised. Two methods for organising these cell types are explored.
One is the artificial classification technique, clustering cells using commonly accepted criteria of similarity. The
second approach, an empirical method modeled after cladistics, resolves the classification in terms of shared
features rather than overall similarity. While the results of each scheme differ, both methods address important
questions. The artificial classification provides compelling (and independent) support for the neural crest as the
fourth germ layer, while the cladistic approach permits the evaluation of cell type evolution. Using the cladistic
approach we observe a correlation between the developmental and evolutionary origin of a cell, suggesting that
this method is useful for predicting which cell types share common (multipotential) progenitors. Whereas the
current effort is restricted by the availability of phenotypic details for most cell types, the present study demon-
strates that a comprehensive cladistic classification is practical, attainable, and warranted. The use of cell types
and cell type comparative classification schemes has the potential to offer new and alternative models for
therapeutic evaluation.

Key words : cell evolution, cell homology, germ layer, neural crest cells, neurons, transdifferentiation.

CONTENTS

I. Introduction ................................................................................................................................................. 426

(1) Previous cell type categorisation schemes .......................................................................................... 427
(2) Cell types and the species analogy ...................................................................................................... 427
(3) Cell type homology ............................................................................................................................... 427
(4) Human cell types .................................................................................................................................. 428
(5) Development of human cell types ...................................................................................................... 428
II. Experimental procedures ............................................................................................................................ 430
(1) The data set ........................................................................................................................................... 430
(2) Methodological approach – classification schemes ........................................................................... 430
III. Results ........................................................................................................................................................... 431
(1) The updated list of cell types ............................................................................................................... 431
(2) Artificial classification of all cell types ................................................................................................ 433
* Author for correspondence : Tel : (902) 494-3335 ; Fax : (902) 494-3736 ; E-mail : mvickary@dal.ca
426 Matthew K. Vickaryous and Brian K. Hall

(3) Cladistic classification of neural-crest-derived cells .......................................................................... 434

(4) Comparison : artificial versus cladistic .................................................................................................. 434
IV. Discussion ..................................................................................................................................................... 434
(1) Application of the cladistic technique ................................................................................................ 434
(2) Employment of cell types and cell type classification schemes ....................................................... 436
(3) Neural crest as the fourth germ layer ................................................................................................. 437
(4) The evolution of cell types ................................................................................................................... 438
V. Areas for future research ............................................................................................................................ 440
VI. Conclusions .................................................................................................................................................. 440
VII. Acknowledgements ...................................................................................................................................... 441
VIII. References .................................................................................................................................................... 441

I. INTRODUCTION expression, membrane properties and the pattern of firing

All organisms are composed of cells, minute compartments
of fluid matrix with various chemical components shrouded
in a limiting membrane (Alberts et al., 1989). Whereas no
two cells are identical in appearance, generalized patterns of
morphology and biochemistry suggest that all cells conform
to a relatively limited number of patterns (Willmer, 1970;
Alberts et al., 1989 ; Valentine, 2003 ; see also Tyner, 1975;
Rowe & Stone, 1977 ; Rodieck & Brening, 1983). These
limited patterns of diversity are referred to as cell types.
Along with other mutable biological units such as genes
and species, cell types exist in nature but remain notoriously
difficult to define precisely and unambiguously (Valentine,
2002, 2003). Consequently, consensus on how many cell
types exist in multicellular organisms such as humans
remains unclear.
In an operational sense cell types, like species, are gener-
ally treated as numerically restricted entities. While most
authorities (e.g. Alberts et al., 1989; Valentine, 2002, 2003)
acknowledge that some degree of variation exists between
any two members of the same cell type, there is a consensus
that cell type morphology, cytoanatomy, molecular biology,
and biochemistry are not infinite. As observed by Alberts
et al. (1989, p. 995) ‘there is no continuum of adult cell
types intermediate in character ’. Herein, the issues of how
to classify cell types and what these schemes have to offer
evolutionary biologists are investigated using a newly com-
piled catalogue as the source of data.
According to Maclean & Hall (1987, p. 13) cell types may
be described as ‘different classes or kinds of differentiated
cells ’. Traditionally, recognition and characterisation of
cell types have been based on morphological characters
visible using light and electron microscopy (Bell & Mooers,
1997; Valentine, 2002, 2003). Those features, including
cell, organelle, and inclusion size, shape, staining properties,
cytoskeletal architecture, surface structures, and – in the
case of organelles and inclusions – relative number and dis-
tribution, are commonly supplemented with data pertaining
to function and topography (Maclean & Hall, 1987). More
recent techniques discriminating cell types include enzyme
histochemistry, antibody labeling, and gene expression
data. In the case of neurons, the identification of cell types
(sometimes referred to as neuron species) may also include
the distribution of input and output synapses, protein
(e.g. Somogyi & Klausberger, 2005; Toledo-Rodriguez
et al., 2005). In accordance with the current emphasis on
molecular biology, cell types have also been defined by gene
expression patterns that give rise to a particular phenotype
(Arendt, 2003). As will be discussed however, this overlooks
the role of epigenetic factors. Perhaps ideally, one or more
unique cell markers, molecules demonstrating unambiguous
evidence of identity and relationship, would characterise
each cell type. Regrettably however, in many instances
such putative ‘ markers’ are neither unique nor evidence for
terminal differentiation (Adler, 2005).
All these methods require that cells (and thus cell types)
are static, terminally differentiated entities. However, cells
are not developmentally static. Indeed cells, like organisms,
undergo changes during their life span until their death and
few cells can truly be considered incapable of undergoing
further re- and dedifferentiation events – particularly in vitro
(Hall, 1970; Alberts et al., 1989; Fedak et al., 2002). Also,
as stated above, cells within a given cell type population
inevitably demonstrate some degree of morphological
variability (Valentine, 2003). Furthermore, cell type identity
is complicated by unusual cells that share features with
two or more routinely encountered cells. For example, the
myofibroblast is a fibroblast-like cell found at sites of wound
healing that expresses a-actin otherwise typical of smooth
muscle cells. Finally, cells and cell types evolve (Fedak et al.,
2002; Arendt, 2003; see below). Consequently, acceptance
of a cell as an identifiable kind is often at the discretion (and
opinion) of the author (Bell & Mooers, 1997). As stated
by Rodieck & Brening (1983, p. 121) ‘ [d]iscovery [of cell
types] is often a creative act ’.
Clearly characterising a cell as a cell type is not a
simplistic task. It is not enough for a particular cell to
share a similar morphology, function, and set of biochemical
properties with a given (i.e. named, identified, recognised)
cell type. As noted by Maclean & Hall (1987), several other
conditions need to be met :
(1) All cells under consideration should be at the same
stage of the cell cycle (gap phase 1, synthesis phase, gap
phase 2, or mitosis). During the cell cycle there are con-
siderable differences in the amounts of protein, RNA and
DNA synthesised, and overall cell morphology and size are
subject to change (Alberts et al., 1989). With few exceptions
(e.g. osteoclasts), most cells ultimately enter senescence
and die.
Human cell types
(2) All cells under consideration should be at the same
stage of ontogeny or maturation. Cells have limited life
spans and may demonstrate some morphological differences
throughout their existence. Cells representing stem or un-
differentiated states, by definition, should not be considered
or included as discrete cell types. Such progenitor or tran-
sitional states are subsumed into the listing as constituent
members of differentiated cell type lineages.
(3) If cells are to be compared between individuals, the
chronological age of each participant should be congruent.
To these caveats the following additions should be added :
(4) All cells under consideration should be obtained from
in vivo, not in vitro, sources. Many cells change both their
morphology and their biochemical products considerably
if maintained in culture. Chondrocytes placed in culture
lose their rounded appearance, stop producing type II
collagen, and come to resemble flattened fibroblasts ; ulti-
mately they begin to produce type I collagen (Alberts
et al., 1989; see also Nelander, Mostad & Lindahl, 2003).
(5) If cells are to be compared between individuals, then
the sex of each participant may need to be considered. In
sexually reproducing organisms there are obvious differ-
ences in both the cells supporting the gametes (within the
reproductive organs) and in the gametes themselves, as well
as cells that are sex-hormone dependent.
(1 ) Previous cell type categorisation schemes
One of the earliest efforts to establish practical groupings
of cells comes from the work of Schwann (1839). Famous
for his elaboration with Schleiden of the cell theory
(Mazzarello, 1999), Schwann proposed a five-group classi-
fication scheme for tissue types that effectively established
our modern view of cell categorisation. His categories
included isolated/independent cells (blood and lymph),
independent cells in combination (epithelium), cells welded
by intercellular substance (bone, enamel), fibre cells (tendon,
loose connective tissue), and cells whose walls have broken
down and whose cavities have run together (muscles, blood
vessels, nerves) (Schwann, 1839, as cited in Hall, 1969).
More recent efforts have modified this scheme into a
four-group subdivision consisting of epithelial, muscular,
nervous, and connective tissues (e.g. Junqueira, Carneiro &
Kelley, 1989).
Two intriguing alternatives also deserve mention,
although neither is widely adopted. Willmer (1970) pro-
posed a system wherein progenitor cells were classified based
on morphology and behaviour in culture. This scheme used
characteristics such as the presence of desmosomes, whether
or not the cells are phagocytic, and if the cells persist as
individuals or masses. Willmer’s four-group classification of
the minimum number of progenitor cells includes epithelio-
cytes, mechanocytes (fibroblasts), amoebocytes (wandering
cells) and nerve cells. A scheme presented by Stevens &
Lowe (1997) categorises groups of cell types according to
function (in vivo), resulting in an eight-group subdivision:
epithelial, support, contractile, nerve, germ, blood, immune,
and hormone-secreting cells.
Whereas explicit tabulations are rare in the literature,
most textbooks of histology and cytology do group different
427
cell types under a limited number of headings. For example,
the ultrastructural atlas of human cells by Lentz (1971)
identifies 178 different cell types grouped under 15 headings
related to function, organ system, and/or tissue type. A
more recent assessment of human cell type categorisation
is found in Alberts et al. (1989) who presented a tabulated
list of 210 human cell types subdivided into 20 categories
(see also Freitas, 1999). As with Lentz (1971) and Stevens
& Lowe (1997), the categories used by Alberts et al. mostly
relate to function.
(2 ) Cell types and the species analogy
Given the vastness of cell types, difficulties arise in how
effectively and efficiently to organise the data set such that
it can be employed to address evolutionary and develop-
mental questions, as well as more clinically related topics
including the discrimination of normal versus abnormal cell
types and cell type distributions characteristic of pathologies
and cancer. The problem becomes – what methods should
be adopted to classify and organise cell types into smaller,
more exclusively nested subsets ? Similar questions have
been considered by molecular biologists, particularly those
concerned with genes and proteins. Among their responses
are various computational sorting techniques such as hier-
archical clustering analysis (recursive partitioning of data
based on multiple variables), principal components analysis
(a multivariate statistical method), and relevance networks
(interconnected associations of seemingly incongruent bio-
logical features, such as gene expression and drug resist-
ance). We employ two alternative approaches familiar to
most organismal biologists. Drawing on the notion that cell
types represent (by definition) (terminally) differentiated
states (i.e. end points), and that ultimately all cell types are
derived from a single source, the zygote, useful analogies
may be derived from a comparison between the diversity of
cell types and the diversity of organisms (Tyner, 1975 ; Rowe
& Stone, 1977 ; Rodieck & Brening, 1983; Maclean &
Hall, 1987). Biological systematists and taxonomists have
experience in developing, testing and adapting classification
schemes for large data sets. Whereas cell types form tissues,
organs, and organ systems, groups of species form popu-
lations, communities, and ecosystems. As such, the analogy
between cell types and organisms is not only convenient
but practical.
(3 ) Cell type homology
As a matter of convenience, lists of cell types typically
assume that all member cells of a particular cell type (i.e.
those given the same name, e.g. chondrocytes) are hom-
ologous, regardless of germ layer origin or topographic
position. However, this notion is not universally accepted
(e.g. Wolpert, 1969 ; Lewis & Wolpert, 1976 ; see also
Maclean & Hall, 1987 ; Alberts et al., 1989), and it is accurate
to state that, e.g. a chondrocyte is not a chondrocyte on
the basis of : differences in responsiveness to hormones
(e.g. pubic symphysis chondrocytes); morphology (articular
surface chondrocytes) ; rates of growth (nasal septum carti-
lage chondrocytes) ; and/or extracellular matrix products
428
(thyroid cartilage chondrocytes) (Hall, 2005). Whereas
cell types in both the developing forelimbs and hindlimbs
form muscle, cartilage, and bone, each population of tissue-
forming cells is considered to be nonequivalent (Alberts et al.,
1989). Developing limb buds must be specified as either
forelimb or hindlimb. In mice and the domestic fowl, the
gene encoding the Tbx5 transcription factor is expressed in
forelimbs, while the hindlimbs express the related gene
Tbx4 (Gilbert, 2003). Thus, it could be argued that by
definition, these expression patterns indicate that the cell
types of each region are not homologous. Recent molecular,
biochemical, embryological, and physiological experiments
illustrate that even among cells of a particular anatomical
locale, all attributed to the same type, there are differences
in inductive influence and responsiveness to chemical signals
(Alberts et al., 1989).
The task of interpreting cell homology is further compli-
cated by selective affinity. As cells differentiate they become
increasingly discriminatory or selective with regard to
their cellular associations. Whereas cells from a common
embryological origin (e.g. mesoderm) will initially associate,
as differentiation proceeds they become increasingly selec-
tive, with chondrocytes sorting out from skeletal myocytes.
This selective affinity also occurs within developing lineages,
such that fully differentiated cells will not associate with their
(undifferentiated) precursors (Maclean & Hall, 1987).
Admittedly, all members of a named cell type (as for each
species) are not identical. However, not being identical is
not the same as not being homologous. And even while a
particular cell type may arise from more than one develop-
mental origin (e.g. chondrocytes from mesoderm or the
neural crest), as observed by Hall (1995, 2005), homology
is a statement of pattern and not process. Cell types may
themselves be homologous (e.g. all osteocytes are hom-
ologous as cells) and yet nonequivalent at the population
level (not homologous at the level of tissues or organs) (see
also Maclean & Hall, 1987). Similarly, the same cell type
(with common functions, morphologies and distributions)
can be recognised in different taxa. For instance, Gall et al.
(1986) identified peripolar cells in the kidneys of 17 different
species of mammals, including humans, giraffes, and the
platypus. Morphologically, these cells also resembled peri-
polar cells previously described for amphibians.
(4 ) Human cell types
Without question, no other taxon has received as much
active and historical interest in the identification of cell
types and cell type diversity as Homo sapiens. As much of
this attention has come from specialised clinical studies, it
may be argued that, at least in some instances, the degree
of atomization is overly generous (McShea, 1996). Further-
more, outside of anthropology, palaeoanthropology, and
primatology, humans are not commonly considered as
model organisms for the study of evolution. As observed
by Slack (1985, p. 463) ‘Although it is quite common to
mount a search for an animal model which manifests a
disease or condition of Man, it is perhaps less usual to do
the reverse ’. Nevertheless, employment of Homo sapiens
as a model for evaluating cell type diversity is sensible,
Matthew K. Vickaryous and Brian K. Hall
convenient, and therapeutically self-serving. Although the
number of relevant examples is great, one topical case
in point concerns the importance of understanding the
local microenvironment or niche that surrounds stem cells.
Various studies have now demonstrated that stem cell
identity is influenced by the identity of adjacent cell types
(Spradling, Drummond-Barbosa & Kai, 2001; Powell,
2005; Taichman, 2005).
( 5) Development of human cell types
As in all sexually reproducing metazoans, the entirety of
human cell type diversity begins from a single newly formed
cell, the totipotent zygote. The zygote undergoes a series
of repeated mitotic divisions – cleavage – dividing into pro-
gressively smaller daughter cells or blastomeres (numbering
two, then four, eight, etc …). Unique to mammals, cleavage
produces a compact ball of cells (the morula) that develop
a fluid filled space segregating the blastomeres into two
groupings – an outer assemblage surrounding (thus inter-
nalising) an inner cluster (Moore & Persaud, 1993). The
outer assemblage is called the trophoblast, and will ulti-
mately give rise to the chorion (an extraembryonic organ,
precursor of the placenta). The smaller, internal grouping of
blastomeres, the inner cell mass or embryoblast, contributes
to the embryo proper, as well as to extraembryonic organs
such as the yolk sac, allantois, and amnion. Following
implantation into the uterine wall, the embryoblast becomes
reconfigured to form a bilaminar embryonic disc. The layer
of the embryonic disc called the embryonic epiblast provides
the majority of the cells contributing to the embryo proper.
During the earliest stages of gastrulation two germ layers
of the epiblast are established, beginning with ectoderm
and endoderm. A third germ layer, mesoderm, forms
secondarily (see below ; Hall, 1999, 2000). Shortly there-
after, during neurulation, a fourth germ layer arises, the
neural crest. All the somatic cell types of the human body
arise from one of these four pluripotent germ layers, the
ectoderm, endoderm, mesoderm, and neural crest.
However, human cell type diversity is not strictly
achieved by a simple unidirectional pathway, zygotepgerm
layerpcell type (see Table 1). In some instances one differ-
entiated cell type may convert to a second differentiated
cell type, a process generally referred to as either trans-
differentiation or metaplasia (the latter term often is restric-
ted to pathological transformations or alterations in
identity at the level of tissues). This phenotypic conversion
may either be direct (without de-/re-differentiation and
without mitosis) or indirect (with de-/re-differentiation and/
or mitosis) (Slack & Tosh, 2001). Thus, even once differ-
entiated, many cell types remain phenotypically plastic
(Eisenberg & Eisenberg, 2003).
An alternative pathway giving rise to cell types occurs
in the caudalmost region of the embryo, the tail bud or
caudal eminence, and during regeneration. As has now
been demonstrated for representatives of all major ver-
tebrate lineages (including humans), cells from the caudal
region of the embryo develop without the formation of germ
layers, beginning instead as an ectodermally covered hom-
ogeneous cluster of mesenchymal cells – a blastema (Hall,
Human cell types
Table 1. Pathways to cell type diversity
Gastrulation :
zygotepgerm layerpcell type
Secondary development/neurulation :
zygotepblastemapcell type
Direct transdifferentiation (=cellular metaplasia) :
zygotepgerm layerpcell type 1 – cell type 2
Indirect transdifferentiation :
zygotepgerm layerpcell type 1 – de-/re-differentiation/mitosis – cell type 2
Stem cell :
zygotepgerm layerpstem cell1pasymmetric mitosispcell type+stem cell
Hybrid cell2 :
zygotepgerm layerpcell type 1+cell type 2 (or cell type 1 ?)pformation of synkaryonpmitosisphybrid cells
1
There is evidence to suggest that stem cells are capable of transdifferentiation, particularly in response to environmental influence
(see text for details).
2
Although it remains unclear if humans acquire any cell types by spontaneous non-pathologic cell hybridization, giant syncytial cells (e.g.
multinucleated osteoclasts) may represent a special instance of cell hybridization between members of the same cell type that fail to undergo
mitosis (see text for details).
1998 b, 2005 ; O’Rahilly & Müller, 1999 ; Handrigan, 2003).
Neurulation of the caudal region occurs as cells from
the blastema coalesce, giving rise to a solid cord that later
cavitates to form a neural tube, a process referred to as
secondary neurulation (in opposition to primary neurulation
involving gastrulation). For humans, the secondary neural
tube joins with the rest of the presumptive central nervous
system at the level of the second sacral vertebra (O’Rahilly
& Müller, 2002). In addition to the caudal portion of the
neural tube, cells of the blastema differentiate and con-
tribute to the hindgut, blood vessels, somites, trunk neural
crest cells, and the notochord (Hall, 1998b ; O’Rahilly &
Müller, 1999). Formation of a blastema-like mass of de-
differentiated cells is also characteristic of regeneration, such
as following amputation of the fingertip of young children
(Hall, 2005).
In adults there are also populations of stem cells, i.e.
non-differentiated cells that (re)supply differentiated cells
(Maclean & Hall, 1987). Stem cells are multipotent, typically
generating a particular tissue lineage of cells (e.g. lymphoid
progenitors give rise to both T and B lymphocytes;
Eisenberg & Eisenberg, 2003). They may also be capable
of transdifferentiation – converting from one cell lineage to
another ; e.g. neural stem cells into endothelial stem cells
(Wurmser et al., 2004 ; see also Slack, 1985; Slack & Tosh,
2001). Furthermore, there are numerous examples of
specific cell types (e.g. chondrocytes) arising from multiple
sources (e.g. during development from mesoderm and
neural crest ; from a regeneration blastema, and/or by de-
differentiation) and progenitor cells that are capable of
giving rise to more than one mature (differentiated) cell
type (see below).
One last developmental pathway deserves mention. At
least in vitro, it is possible to hybridize different somatic cells.
In most (virtually all ?) instances, hybrid cells – mononuclear
(synkaryon) cells resulting from the fusion of two or more
different cells – are the product of extrinsic manipulation
429
(e.g. treatment with an inactivated virus). It has been
suggested however, that giant syncytial cells, such as multi-
nucleated osteoclasts, represent a form of in vivo spon-
taneously developing cell hybrid (Ringertz & Savage, 1976),
albeit one wherein nuclear fusion and mitosis are arrested
(resulting in the formation of a heterokaryon). Similarly,
multinucleated muscle fibres (myotubes), developing from
the coalescence of numerous mononuclear skeletal muscle
cells, may also represent a form of spontaneously developing
cell hybrid. To make matters more complicated, in human
jaw muscles the multinucleated (hybrid) cells may demon-
strate the presence of multiple myosin heavy-chain protein
isoforms (Korfage et al., 2005), creating a hybrid form of
a hybrid cell. Another possible example of a syncytial
(heterokaryon) cell hybrid is the syncytiotrophoblast, a
multinucleated mass that facilitates the implantation of the
blastocyst into the uterine wall. However, notwithstanding
the aforementioned, support for cell hybrids as non-patho-
logical, naturally occurring entities seems to be limited.
As all somatic cells within a multicellular organism begin
from a morphologically homogeneous population that con-
tains the same genome, cell fate (and differentiation into
a particular cell type) is a consequence of the combination
of epigenetic factors and gene expression. Whereas some
RNAs and proteins are common to many cells (e.g. cyto-
skeletal proteins), others are exclusive (cell markers, such as
haemoglobin in red blood cells). Moreover, even among the
commonly produced molecules, the amounts synthesised
and stored differ between various cell types. Thus, differ-
ences in amounts and patterns of gene expression have
the potential to offer a unique descriptor for each cell type,
albeit one that is sensitive to changes in the cell cycle or
the age of the cell (Nelander et al., 2003; Sarwal & Alemi,
2005). Recent work by Jongeneel et al. (2005) has deter-
mined that differences in gene expression profiles between
various cell types are largely regulated by a relatively limited
number of cell-type-specific genes.
430
The generation of phenotype however, is not only a
function of the genomic blueprint. Interfacing with and
moulding the outcome of gene expression are epigenetic
factors. Although various interpretations of the term ‘epi-
genetic ’ exist (reviewed by Müller & Olsson, 2003), we are
particularly concerned with the sum of all internal (embry-
onic ; including covalent modifications of the chromatin
configuration that transcriptionally silence genes) and ex-
ternal (environmental) factors. As such, epigenetic factors
may include maternal cytoplasmic contributions, cell and
tissue dynamics, DNA methylation, histone modification,
imprinting, temperature, humidity, and nutrient levels
(Müller & Olsson, 2003 ; see also Hsieh & Gage, 2004,
2005). Some, including DNA methylation and histone
modification, may be inherited. Others, for example mech-
anical influences and temperature, are condition specific.
However, all contribute to cell type specificity.
II. EXPERIMENTAL PROCEDURES
(1 ) The data set
The updated registry of human cell types presented herein
(Appendix 1) was created by consulting a variety of sources
from the literature, including Lentz (1971), Solcia et al.
(1987), Alberts et al. (1989), Anderson (1989), Campbell et al.
(1989), Matthews (1989), Yelnik et al. (1991), Kolb, Lindberg
& Fisher (1992), Dacey (1994), Mugnaini & Floris (1994),
Ostapoff, Feng & Morest (1994), Kiernan (1998), Caterina
& Julius (1999), Sanders et al. (1999), Canning & Fischer
(2001), Cant & Benson (2003), Somogyi & Klausberger
(2005), and Yáňez et al. (2005). The catalogue was initially
assembled assuming that all cell types recognised in the
literature are natural entities (i.e. exist independent of
investigation and investigator ; Rodieck & Brening, 1983).
In addition, this rationale draws attention to even poorly
known and weakly supported cell types, with the expectation
that future investigations will provide more definitive evi-
dence supporting (or refuting) such claims (see also Rodieck
& Brening, 1983). The composite data set was then modified
as follows :
(1) Any cell types identified as stem or immature
members of a particular cell type lineage were removed.
(2) Redundant cells (cells present on more than one list)
were removed so that each cell type was represented only
once.
(3) In situations where the single inclusive cell type of
one (group of ) author(s) represented several exclusive
cell types of another (group of ) author(s), the default was to
accept the largest number of subdivisions as the actual
number of cell types, except in situations that contradicted
statement 1 (above). For example, Lentz (1971) listed four
different cell types corresponding to stages in the maturation
series of an epithelial keratinocyte. Since these ‘ cell types ’
are deemed to represent immature members of the epi-
thelial keratinocyte lineage, only one cell type (epithelial
keratinocyte) is retained. Similarly, erythrocytes are a single
cell type.
Matthew K. Vickaryous and Brian K. Hall
( 2) Methodological approach – classification
schemes
As noted previously, for the purposes of categorisation, a
parallel may be drawn between cell types and species.
Species arguably represent the most fundamental classifi-
cation unit in biology (at least from the viewpoint of bio-
diversity) and while consensus on how to define the term
is lacking (there are as many as 20 different species con-
cepts ; Harrison, 2002), some of the most popular concepts
rely on character-based definitions – observed similarities
between two or more entities. Two approaches, artificial
classification and cladistics, receive attention here.
Artificial or key classification is a tool of convenience
often employed to identify an unknown from a previously
established registry. In this context, artificial refers to an
unnatural arrangement that does not exist beyond human
perception. For units such as cell types, readily observed
phenotypic characters (morphological, biochemical, or
otherwise observable features) permit the unknown to be
sequentially sorted into increasingly more exclusive and
nested subgroups (e.g. epithelial cells separated from
nervous tissue cells). Mayr & Bock (2002) identified this
variety of ordering system as a ‘ downward classification ’,
whereby an initial grouping is divided in a step-wise
fashion into smaller clusters. It is important to recognise
that as the selection of partitioning characteristics is
arbitrary – albeit convenient – such features do not reflect
homologies.
Arguably, the artificial classification scheme resembles a
decision tree. However, unlike many decision trees, our
artificial scheme is not reliant upon algorithms ; cell types are
organised based on a predetermined series of hierarchical
a priori decisions. Beginning with the cell as a component
of one of the four basic tissue types (epithelial, nervous,
muscular, and connective tissue; the ‘ special purpose ’
criterion of Mayr & Bock, 2002), subsequent decisions
were based on histological/cytological characterisations
commonly used to describe cells. These criteria included
the relative position of a cell to other anatomical structures
(e.g. covering or lining), function (e.g. support or blood/
immune), and biochemical product (e.g. mucous or seb-
aceous). Inherently, such decisions are fraught with subjec-
tivity. In an attempt to remain conservative, in this analysis
these decisions were made in consultation with traditional
human histological texts (e.g. Rhodin, 1974 ; Bloom &
Fawcett, 1975), as well as the different classes of cell types
presented by Lentz (1971), Alberts et al. (1989), and
Campbell et al. (1989).
For the purposes of organisation artificial classifications
are often represented as dendrograms. When completed, the
structure of the catalogue is reflected by the topography of
the dendrogram. Arrangements of cell types closely linked
in the dendrogram are considered to be more pheno-
typically similar than cell types that were separated earlier
during the sorting process. Once established, artificial
classifications have the advantage of permitting consistent,
systematic, and reproducible groupings of an unknown unit
(e.g. species or cell type). However, they do not (necessarily)
reveal developmental (or evolutionary) origins (e.g. more
Human cell types
than one cell type may be derived from a common
multipotential precursor, a pattern of descent not always
reflected by the dendrogram).
The alternative approach is to categorise cell types on the
basis of shared-derived characteristics or synapomorphies.
Cladistics (a term often used synonymously with phylogen-
etic systematics) is a comparative technique that assumes
all units under consideration are, in some fashion, related
to each other, and that the genealogy of the units may be
recovered by analysing intrinsic (and inherited) characters.
More specifically, the relationship between compared units
is gleaned from the study of shared-derived characters –
synapomorphies – considered to represent homologies.
For cell types, species and the like, it is predicted that closely
related units share one or more derived characters, to the
exclusion of more remotely related units. In the (likely) event
that data appear to conflict, the most parsimonious
arrangement (requiring the fewest assumptions) is usually
taken to be the most likely arrangement. In the interests
of efficiency, computer programs (typically involving a
parsimony algorithm) carry out the cladistic analyses.
Cladograms are testable hypotheses based on numerous
sources of transparent data. As such they can be readily
examined and tests can be repeated with (or without)
the addition or subtraction of information. Furthermore,
cladograms are extremely responsive to such modifications
to the original data set (Stone, 1996). Interestingly, this
scheme accurately approaches the concept of a testable
method (based on multiple sources of data) for classifying
cell types first suggested by Rowe & Stone (1977), work that
pre-dates widespread adoption of cladistic methods. As
they note, one of the main advantages of such a method is
that it permits the classification to be modified with experi-
ence and the addition of new data.
The pattern of clustering may be displayed as a series of
nested boxes or ellipses (a Venn diagram), although it is
typically depicted as a branching diagram or cladogram,
similar to the classification dendrogram. Also similar to
the classification dendrogram, selection of synapomorphic
features used in the cladistic analysis is a priori. However,
unlike the classification dendrogram, interpretation of the
topography of the cladogram is a posteriori. The resulting
cladogram demonstrates an interpretation of common
descent based on the pattern of shared-derived features. In
the present study, the cladogram of cell types (representing
the cladistic classification) is used to interpret the pattern of
cell type interrelationships.
Although some cell types are the focus of considerable
attention, most linger in relative obscurity. Thus, infor-
mation for analysing interrelationships between large
numbers of cell types is limited. In our analysis, only eight
types of cells (plus one outgroup ; see below) were con-
sidered, all of which are derivatives of the neural crest germ
layer (sensu Hall, 1998a, 1999, 2000; see below). Owing to
the availability of data, strictly speaking some of these cells
(e.g. sympathetic neurons) may represent groups and not
necessarily a single cell type. In addition, for other cells
immature members of the lineage were included in the
scoring (e.g. for some characters features of osteoblasts were
scored for osteocytes).
431
Nineteen characters were scored (Appendix 2). The
selection of characters is essentially arbitrary, although
each must be shared by at least two cell types. For the
purposes of this analysis, many of the characters listed
were gleaned from written descriptions of cell types from
various histological sources; e.g. Paulsen (1993, p. 307)
describes chromaffin cells as ‘… contain[ing] large nuclei,
abundant electron-dense secretory granules …, a well-
developed Golgi complex, a few profiles of RER [rough
endoplasmic reticulum], and many oval mitochondria ’.
Other characters are related to the sites of neural crest origin
and migration, and reactions with antibody labels.
In order to evaluate if particular cell characteristics were
derived during differentiation (as opposed to already present
in the embryonic germ layer precursor), an undifferentiated
neural crest cell was used as the outgroup to polarize the
character states. A complete matrix of character states used
in this analysis is presented in Appendix 3. The computer
program Phylogenetic Analysis Using Parsimony (PAUP*
4.0b10 ; Swofford, 2000) was employed to evaluate the
character state data, using the branch and bound search
algorithm to find an exact solution. The analysis was opti-
mized to favour both reversals over parallelisms (a so-called
accelerated evolutionary transformation or ACCTRAN)
and parallelism over reversals (a delayed evolutionary
transformation or DELTRAN).
III. RESULTS
(1 ) The updated list of cell types
Although there may be many tens of trillions of cells in a
mature human body (including 1012 glial cells and 1011
neurons in the brain alone; Gilbert, 2003), the most com-
prehensive published tabulation of cell types suggests
that there are only some 210 varieties (Alberts et al., 1989).
However, while this list is extensive, it is by no means
complete; a recent calculation by Freitas (1999) suggests a
theoretical maximum of 370 cell types in humans. Indeed,
as Alberts et al. (1989) admit to making no attempt to
identify all the various types of neurons and other
nervous system cell types, their catalogue grossly under
represents this group of cell types. As estimated by
Bonner (1988) and Valentine (2002), there may be as many
types of neurons as there are other types of cells. In support
of this claim, a recent summary identified 14 types of
neurons from the enteric nervous system of the guinea
pig small intestine, each with a unique combination of
morphological and biochemical properties (Furness, 2000).
Other data suggest that smooth muscle cells and fibroblasts
may also represent an uncalculated diversity of cell types
(Maclean & Hall, 1987 ; Alberts et al., 1989 ; Fries et al.,
1994 ; Freitas, 1999).
Our revised data set yields a total of 411 cell types present
in normal, healthy (i.e. free from pathology) human adults
(Tables 2–5, organised by germ layer of origin ; Appendix 1).
All but two of the cell types are somatic. As previous cell
type inventories have generally neglected nerve cells, the
tabulation of 145 neuron types (representing almost one
432
Table 2. Alphabetical listing of 211 adult Homo sapiens cell types derived from ectoderm (including two cell types derived from
both ectoderm and endoderm). Abbreviations : FSH, follicle stimulating hormone ; MSH, melanocyte stimulating hormoe ;
TSH, thyroid stimulating hormone
ectoderm
astrocyte, fibrous
astrocyte, protoplasmic (velate)
Boettcher cell
choroid plexus cell
ciliary pigmented epithelial cell
ciliary unpigmented epithelial cell
Claudis cell
columnar cell with microvilli
columnar cell without microvilli
cone photoreceptors, blue sensitive
cone photoreceptors, green sensitive
cone photoreceptors, red sensitive
dark cell, crista ampullaris
dark cell, endolymphatic sac
duct cell, intercalated, salivary gland
duct cell, nonstriated
duct cell, striated, salivary gland
ependymal cell
epithelial cell, anterior lens
epithelial cell, conjunctival
epithelial cell, olfactory, olfactory cell
epithelial cell, olfactory, supporting
epithelial cell, olfactory, sustentacular cell
gland cell, Bowman’s dark
gland cell, Bowman’s light
gland cell, ceruminous
gland cell, lacrimal
gland cell, mammary
gland cell, Moll
gland cell, salivary, mucous
gland cell, salivary, serous
gland cell, sweat, apocrine
gland cell, sweat, eccrine clear
gland cell, sweat, eccrine dark
gland cell, von Ebner’s
hair cell, cortical
hair cell, cuticular
hair cell, cuticular, root
hair cell, external
hair cell, Henle’s layer
hair cell, Huxley’s layer
hair cell, medullary
hair cell, organ of Corti, inner
hair cell, organ of Corti, outer
hair cell, shaft
hair cell, sheath
hair cell, type I
hair cell, type II
hyalocyte, vitreous body of eye
interdental cell
keratinocyte
lens fibre cell
light cell
Merkel cell, epidermis
Muller cell
myoepithelial cell
neuron, amacrine cholinergic stratum 2
neuron, amacrine cholinergic stratum 4
neuron, amacrine semilunar type 1
Matthew K. Vickaryous and Brian K. Hall
neuron, amacrine semilunar type 2
neuron, amacrine small-field diffuse
neuron, amacrine spiny
neuron, amacrine stellate-varicose
neuron, amacrine thorny type 1
neuron, amacrine thorny type 2
neuron, amacrine tristratified
neuron, amacrine type A1
neuron, amacrine type A2
neuron, amacrine type A3
neuron, amacrine type A4
neuron, amacrine type A5
neuron, amacrine type A8
neuron, amacrine type A12
neuron, amacrine type A13
neuron, amacrine type A14
neuron, amacrine type A17 spidery-diffuse
neuron, amacrine type A18
neuron, amacrine type AII
neuron, amacrine wavy
neuron, amacrine wiry
neuron, amacrine wooly diffuse
neuron, antenniform cell
neuron, axo-axonic
neuron, back-projection
neuron, basket cell type I
neuron, basket cell type II
neuron, basket cell type III
neuron, Betz cell
neuron, bilaminar
neuron, bistratified
neuron, bistratified giant bipolar
neuron, blue cone bipolar cell type a
neuron, blue cone bipolar cell type b
neuron, CA1 oriens alveus interneuron
neuron, CA1 pyramidal
neuron, CA3 pyramidal
neuron, cell of Martinotti
neuron, chandelier
neuron, clavate cell
neuron, dentate granule cell
neuron, diffuse cone bipolar cell type a
neuron, diffuse cone bipolar cell type b
neuron, double bouquet cell (DBC)
neuron, elongate cell
neuron, flat midget bipolar
neuron, fusiform cell
neuron, ganglion G3
neuron, ganglion G4
neuron, ganglion G5
neuron, ganglion G7
neuron, ganglion G8
neuron, ganglion G10
neuron, ganglion G11
neuron, ganglion G12
neuron, ganglion G16
neuron, ganglion G17
neuron, ganglion G19
neuron, ganglion G20
neuron, ganglion G21
neuron, ganglion G22
neuron, ganglion G23
neuron, ganglion M
neuron, ganglion P1
neuron, ganglion P2
neuron, giant cell
neuron, giant diffuse bipolar
neuron, globular bushy cell
neuron, Golgi cell
neuron, granule cell
neuron, hippocampal-septal
neuron, horizontal type HI
neuron, horizontal type HII
neuron, horizontal type HIII
neuron, interneurone specific cell I (IS-I)
neuron, interneurone specific cell II (IS-II)
neuron, interneurone specific cell III
(IS-III)
neuron, interplexiform
neuron, invaginating midget bipolar
neuron, lacunosaum-moleculare perforant
path associated
neuron, lacunosaum-moleculare-radiatum
perforant path associated
neuron, large spherical bushy cell
neuron, mitral cell
neuron, motor, A-alpha (IA)
neuron, motor, A-gamma
neuron, neostriatal cholinergic interneuron
neuron, neurogliaform cell
neuron, nigral dopaminergic cell
neuron, octopus cell
neuron, olfactory
neuron, olfactory bulb granule cell
neuron, olfactory cortex interneuron (deep)
neuron, olfactory cortex interneuron
(superficial)
neuron, olfactory cortex pyramidal cell
neuron, stratum oriens, lacunosum-
molaculare interneuron (O-LM)
neuron, periglomerular cell
neuron, Purkinje cell
neuron, pyramidal cell
neuron, Renshaw cell
neuron, Retzius-Cajal cell
neuron, rod bipolar cell
neuron, Schaffer collateral associated
neuron, small spherical bushy cell
neuron, spinal la interneuron
neuron, spinal motor
neuron, striatal leptodendritic
neuron, striatal microneuron
neuron, striatal spidery
neuron, striatal spiny
neuron, thalamic relay
neuron, thalamic reticular
neuron, tufted cell
neuron, type I stellate cell
Human cell types 433

Table 2 (cont.)

ectoderm

neuron, type II stellate cell
neuron, unipolar brush cell (UBC)
oligodendrocyte, interfascicular
oligodendrocyte, satellite
phalangeal cell, inner supporting
phalangeal cell, outer supporting
pigment epithelial cell, retina
pillar cell, inner supporting
pillar cell, outer supporting
pineal interstitial cell
pinealocyte
pituicyte
pituitary cell, anterior,
adrenocorticotrophic secreting
pituitary cell, anterior, growth hormone
secreting
pituitary cell, anterior, prolactin secreting
pituitary cell, anterior, TSH secreting
pituitary cell, FSH secreting
pituitary cell, intermediate, MSH secreting
pituitary cell, luteinizing hormone
secreting
pituitary folliculo-stellate cell
planum semilunatum cell
rod cell
sebaceous gland cell
secretory cell, oxytocin
secretory cell, vasopression
squamous cell, endolymphatic sac lining
squamous cell, perilymphatic space lining
stellate cell, perilymphatic space lining
stria vascularis basal cell
stria vascularis intermediate cell
stria vascularis marginal cell
supporting border cell
supporting cell, organ of Corti
supporting cell, vestibular apparatus
tanycytes
type I taste bud cell
vestibular apparatus membrane cell

ectoderm and endoderm

epithelial cell, stratified squamous

type II taste bud cell

third of the entire catalogue) is of particular significance.
Amongst the diversity are 25 peripheral nervous system
(enteric, motor, parasympathetic, and sympathetic) neurons,
60 special (visual) sensory neurons and 55 central nervous
system neurons. The list also includes :
(a) Three varieties of mineraloclasts, including multi-
nucleated osteoclasts, mononucleated osteoclasts, and
chondroclasts. Whereas most histology texts only identify
multinucleated osteoclasts, recent work has indicated that
mononucleated osteoclasts are common in mammals and
responsible for finer scale bone resorption than the multi-
nucleated form (see Eckhard, Hansen & Hall, 2001). As our
tabulation only considers adult cell types, we have omitted
odontoclasts (dentinoclasts) and cementoclasts, which are
present during root resorption of the deciduous dentition.
Similarly, ameloblasts (enamel depositing cells present
during tooth formation) were also excluded from the final
list.
(b) Four types of interstitial cells of Cajal (ICC) (see
Appendix 1), pacemaker cells that mediate inputs from
the enteric nervous system to the smooth muscle cells of
the gastrointestinal musculature (Sanders et al., 1999).
Historically these cells have been likened to each of neurons,
smooth muscle cells and fibroblasts.
(c) Five sympathoadrenal (SA, or adrenergic) cell types,
including sympathetic adrenergic neurons, two types of
chromaffin cells (epinephrine and norepinephrine secreting)
and two types of small intensely fluorescent (SIF) cells
(type I cells, the endocrine cell-like form, and type II cells,
the interneuron-like form) (Matthews, 1989).
(d) Fifteen types of gastroenteropancreatic cells, each
secreting a unique combination of one or more peptides
and hormones.
For the sake of completeness, cell types that are exclusive
to either females (e.g. corpus luteal cells), or to males
(prostatic epithelial cells) were included. With few excep-
tions, acceptance of this compilation requires that each cell
type listed is presumed to represent a mature, fully differ-
entiated entity (cells are terminally differentiated) and that
these cells have a stable differentiation. It is worth observing
however that some cell types appear to be phenotypically
transient and develop as a specific response to a particular
condition. For example, López et al. (2004) demonstrated
that renin-secreting cells of the kidney (which function in
regulating blood pressure and electrolytes) differentiate
in response to fluctuations in homeostasis. If homeostasis is
normal, many (although not necessarily all) of these cells de-
differentiate into non-renin-secreting cells such as smooth
muscle or epithelial cells. In addition to renin-secreting cells,
our tabulation includes other ‘ condition-specific’ cells in-
cluding plasmacytoid dendritic cells (dendritic-like cells
formed in response to viral infection) and myofibroblasts
(fibroblast/smooth muscle-like cells present at healing
wounds). Although an effort has been made to provide a
greater representation of neuron diversity, it is also ac-
knowledged that, as for previous cell type catalogues, this
group remains inadequately represented. Moreover no
effort was made to explore fibroblast or smooth muscle
diversity (see Fries et al., 1994; Freitas, 1999).
(2 ) Artificial classification of all cell types
A total of 34 terminal artificial classification categories
(designated A to HH) were obtained, as nested subsets of
the original fourfold polychotomy. The resulting artificial
classification scheme is presented in Fig. 1. Appendix 1
provides a detailed summary of all cell types included in
each artificially derived category, as well as the germ layer
of origin (ectoderm, endoderm, mesoderm, neural crest,
extraembryonic endoderm, and uncertain germ layer
434 Matthew K. Vickaryous and Brian K. Hall

Table 3. Alphabetical listing of 59 adult Homo sapiens cell types derived from endoderm (including two cell types derived from both
endoderm and ectoderm, one derived from both endoderm and mesoderm, and two derived from extraembryonic endoderm)

endoderm

acinar cell gastroenteropancreatic endocrine cell, gastroenteropancreatic gastrin/

alpha cell
argentaffin cell
beta cell
brush border cell, intestine (with microvilli)
centroacinar cells
chromophobic (C) cell
ciliated respiratory tract cell
Clara cell
delta cell
duct cell, bile duct
duct cell, gall bladder
epithelial cell, intestinal
epithelial cell, lung (pulmonary)
epithelial cell, prostatic
epithelial cell, respiratory, basal cell
epithelial cell, respiratory, brush cell
epithelial cell, respiratory, ciliated cell
epithelial cell, transitional
epithelial cell, urinary system
epithelial mucous membrane cell
gastroenteropancreatic cholecystokinin
secreting (CCK) cell
P cell
gastroenteropancreatic
enterochromaffin-like (ECL) cell
gastroenteropancreatic gastrin secreting
(G) cell
gastroenteropancreatic glucagon
secreting (A) cell
gastroenteropancreatic glucagon-
dependent insulinotropic peptide
secreting (GIP) cell
gastroenteropancreatic glucagon-like
peptide-2 secreting (GLP-2) cell
gastroenteropancreatic motilin secreting
(M) cell
gastroenteropancreatic neurotensin
secreting (N) cell
gastroenteropancreatic pancreatic
polypeptide secreting (PP) cell
gastroenteropancreatic peptide tyrosine
tyrosine (PYY) secreting cell
gastroenteropancreatic secretin secreting
(S) cell
cholecystokinin secreting (TG) cell
gastroenteropancreatic very large (VL) cell
gastroenteropancreatic X cell
gland cell, Brunner’s
gland cell, bulbouretheral
gland cell, parathyroid
gland cell, prostate
goblet cell
Hassall’s (thymic) corpuscle epithelial cell
hepatocyte
oxyntic (parietal) cell
Paneth cell
pneumocyte, type I
pneumocyte, type II, great alveolar cell
(septal cell)
principal (chief) cell
pulmonary (P) endocrine cell, bombesin
secretory stomach cell
thymic epithelial-reticular (TER) cell
thymocyte
thyroid follicular cell
zymogenic cell

endoderm and ectoderm endoderm and mesoderm extraembryonic endoderm

epithelial cell, stratified squamous podocyte, glomerular epithelial cell oocyte

type II taste bud cell spermatozoa

origin ; see also Tables 2–5) and the traditional tissue type to
which each cell type is commonly assigned.
(3 ) Cladistic classification of
neural-crest-derived cells
The results from our cladistic analysis, presented as a
cladogram of cell type interrelatedness (Fig. 2), finds the
same single most parsimonious outcome (with 29 steps)
from both the ACCTRAN and the DELTRAN optimiz-
ations (consistency index=0.6552 ; retention index=
0.6970 ; rescaled consistency index=0.4566). Notably, there
is no support for a monophyletic lineage of neurons.
Sympathetic neurons are positioned as the sister group to
(chromaffin+parafollicular cells), with sensory neurons as
the next successive outgroup. Osteocytes+chondrocytes
also form a discrete clade.
(4 ) Comparison : artificial versus cladistic
In order to provide a visual comparison between the two
methods, the artificial classification was pruned to include
only those cells participating in the cladistic classification
(Fig. 2). Not surprisingly, the results are incongruent. The
artificial classification finds three main arrangements : epi-
thelial cells ([parafollicular+chromaffin cells]+melano-
cytes); nervous tissue cells ([sensory+sympathetic neurons]+
Schwann cells) ; and non-polarized extracellular matrix se-
creting cells (osteocytes+chondrocytes). By contrast, the
cladistic scheme does not find either the epithelial cell group
or the nervous tissue cell group. Instead, all biogenic amine-
handling cells are clustered, ([parafollicular+chromaffin
cells]+sympathetic neurons), with sensory neurons posi-
tioned outside this cluster, as members of the endocrine
cell lineage. The position of Schwann cells is basal to all
other cell types. However, the non-polarized extracellular
matrix-secreting cell group (osteocyte+chondrocyte) is
recognised.
IV. DISCUSSION
( 1) Application of the cladistic technique
The cladistic technique has previously been employed to
compare a variety of different entities, including species,
genes and DNA sequences, and even mathematical models
(Stone, 1996). For species or other taxonomic units, cladis-
tics assists in the recovery of the pattern of interrelation-
ships and provides a framework for hypotheses concerning
organismal evolution. And just as species (or other taxo-
nomic units) evolve, so do genes and proteins (Pevsner,
2003). Thus, it is not surprising that many molecular
Human cell types 435

Table 4. Alphabetical listing of 105 adult Homo sapiens cell types derived from mesoderm (including one cell type derived from
mesoderm and endoderm and ten derived from mesoderm and neural crest)

mesoderm

adipose cell, brown interstitial cell of Cajal, submucosal muscle cell, cardiac ordinary
adipose cell, lipocyte of liver region (IC-SM) muscle cell, cardiac, nodal heart
brush border cell Kupffer cell muscle cell, satellite, skeletal
cementoblast Langerhans cell, epidermis muscle cell, skeletal, intermediate
chondroclast leukocyte, basophil muscle cell, skeletal, red cell (slow)
ciliated female reproductive cell leukocyte, eosinophil muscle cell, skeletal, white cell (fast)
ciliated male reproductive cell leukocyte, globule muscle spindle, nuclear bag
corpus luteum cell leukocyte, granulocyte muscle spindle, nuclear chain
dendritic cell leukocyte, neutrophils myofibroblast
duct cell, collecting tubule Leydig cell non-ciliated cell, ductuli efferentes
duct cell, ductus epididymidis littorial cell nucleus pulposus cell
duct cell, seminal vesicle and prostate lymphocyte, helper T parietal cell, kidney glomerulus
gland lymphocyte, IgA B peripolar cell
endothelial cell, central nervous system lymphocyte, IgE B plasma cell
endothelial cell, continuous lymphocyte, IgG B plasmacytoid dendritic cell
endothelial cell, corneal lymphocyte, IgM B principal cell, epididymis
endothelial cell, fenestrated lymphocyte, killer cell Purkinje fibre cell
endothelial cell, lymphatic lymphocyte, killer T secretory cell, renin
endothelial cell, splenic lymphocyte, suppressor T secretory endometrial cell
epithelial cell, distal tubule macrophage, alveolar secretory fallopian tube cell
epithelial cell, proximal tubule macrophage, connective tissue secretory seminal vesicle cell
epithelial cell, thick loop of Henle macrophage, multinucleated serosal cell
epithelial cell, thin limb loop of Henle macrophage, serous cavity Sertoli cell
erythrocyte macrophage, splenic tenocyte
fibroblastic reticular cell macula densa cell, distal tubule testis interstitial cell
follicle cell mast cell theca interna cell
gland cell, Bartholin’s megakaryocyte zona fasciculata and reticularis cell,
gland cell, Littré mesangial cell glucocorticoid secreting
interstitial cell of Cajal, deep muscularis mesothelial cell zona fasciculata and reticularis cell,
plexus region (IC-DMP) microglia mineralocorticoid secreting
interstitial cell of Cajal, intramuscular monocyte zona fasciculata cell
region (IC-IM) mononucleated osteoclast zona glomerulosa cell
interstitial cell of Cajal, myenteric multinucleated osteoclast zona reticularis cell
region (IC-MY) muscle cell, cardiac fibre
mesoderm and endoderm

podocyte, glomerular epithelial cell

mesoderm and neural crest

adipose cell, white chondrocyte, hyaline cartilage pericyte, blood capillary

chondrocyte, elastic cartilage fibroblast synovial A cell
chondrocyte, fibrocartilage muscle cell, smooth synovial B cell
osteocyte

biologists are familiar with the utility of cladistic analysis as
a means of comparison, and that molecular data (in the form
of DNA, RNA, or protein sequences) has proven to be a
powerful phylogenetic tool. In addition to facilitating the
estimation of genealogy, molecular sequence data are also
used to group genes and proteins into respective families and
understand gene function (Liberles, 2005).
Although we have chosen to focus our analysis on
phenotypic characters, it is worthwhile observing that the
cladistic methodology is well suited to the incorporation of
gene expression data. As discussed above, gene expression
patterns have the potential to provide a unique description
of each cell type. Until recently however, collecting the large
amounts of expression data necessary to compare different
cell types was prohibitively time-consuming. Fortunately,
since the 1990s this particular obstacle has been largely
overcome with the advent and widespread use of DNA
microarrays that permit rapid determination of what genes
(and their relative expression levels) are being transcribed
by a particular cell at a particular moment. Given that the
resulting gene expression profile may consist of information
from thousands of genes, the amount of data is enormous.
436 Matthew K. Vickaryous and Brian K. Hall

Table 5. Alphabetical listing of 47 adult Homo sapiens cell types derived from the neural crest (including ten cell types derived
from both neural crest and mesoderm) and two cell types of uncertain germ layer origin

neural crest

carotid body type I cell
chromaffin cell, epinephrine secreting
chromaffin cell, norepinephrine secreting
enteric (astrocyte-like) glial cell
epithelial cell, stratified squamous corneal
melanocyte
myoepithelial cell, iris
neuron, enteric, interneuron
neuron, enteric, motor to
gastroenteropancreatic endocrine cell
neuron, enteric, motor, excitatory
neuron, enteric, motor, inhibitory
neuron, enteric, secretomotor/vasomotor
neural crest and mesoderm
neuron, enteric, sensory
neuron, enteric, stubby
neuron, parasympathetic, cholinergic
neuron, parasympathetic, non-adrenergic/
non-cholinergic
neuron, sensory, A-beta IB
neuron, sensory, A-beta IIB
neuron, sensory, A-delta cold fibre
neuron, sensory, A-delta type I
neuron, sensory, A-delta type II
neuron, sensory, C-fibre non-peptidergic
neuron, sensory, C-fibre peptidergic
neuron, sensory, mechanoreceptor, other
neuron, sensory, proprioceptor, other
neuron, sensory, warm fibre
neuron, sympathetic, adrenergic
neuron, sympathetic, B-fibre
neuron, sympathetic, C-fibre
neuron, sympathetic, cholinergic
odontoblast
parafollicular (C) cell
satellite cell
Schwann cell
small intensely fluorescent (SIF) cell, type I
small intensely fluorescent (SIF) cell,
type II
squamous cell, pia-arachnoid

adipose cell, white chondrocyte, hyaline cartilage pericyte, blood capillary

chondrocyte, elastic cartilage fibroblast synovial A cell
chondrocyte, fibrocartilage muscle cell, smooth synovial B cell
osteocyte

uncertain germ layer origin

carotid body type II cell

secretory cell, endorphin

In order to manage effectively this quantity of information,
the emerging field of bioinformatics draws upon statistical
algorithms and computational analyses to provide the
necessary tools to exploit even the subtlest gene expression
differences between various cell types.
A word of caution : i.e. in spite of their revolutionary
contributions to molecular biology, microarrays are not
without drawbacks. Gene expression data are sensitive to
changes in the cell cycle and cell ontogeny, and thus rep-
resent extremely specific samples that may not be charac-
teristic of all members of the same cell type. Furthermore,
unless all genes are represented by DNA probes on the
microarray (as a complete reference collection) the gene
expression profile for a given cell type will be deficient and
thus inaccurate. Other possible problems include exper-
imental errors introduced during the hybridization of RNA
to its complement and that cellular RNA production may
be exaggerated compared with the actual proteins pro-
duced, thus gene expression is not (necessarily) correlated to
function (see Sarwal & Alemi, 2005).
(2 ) Employment of cell types and cell type
classification schemes
Despite the fundamental importance of cell types to
histology, cell type catalogues have found only limited
application, typically as a means of organising cells and
tissues for histological perusal. Beginning with the work of
Bonner (1988), cell types were employed to estimate evol-
utionary complexity. According to Bonner (1988), complexity
not only refers to the overall number of integrated parts,
but also alludes to differences in structure and function.
As such, complexity is often framed in a hierarchy, with
each part divisible into various subparts.
Among organisms, Bonner (1988) suggested that one way
to measure complexity is to count the number of cell types.
He cited several examples, ranging from taxa with a single
cell type (bacteria) to those with more than 100 (vertebrates).
Hence, there is a correlation between the advent of the
neural crest germ layer and its cell type derivatives, and
the complexity of craniates (as measured by the overall
number of cell types ; Carroll, 2001). Valentine, Collins &
Meyer (1994) plotted the maximum estimated number of
cell types for a given taxon against a (prehistoric) time scale
and found a quantifiable trend towards increasing the
maximum number of cell types over time.
By contrast, genes do not necessarily provide an index of
evolutionary complexity, as they tend to be conserved and
are not directly related to the number of cell types present
in an organism (Carroll, 2001; Valentine, 2002, 2003).
Although this notion has generally been accepted, some
have cautioned that taxa such as humans have received
relatively rigorous treatment, to the extent of possibly over-
emphasising minor differences between cell types, while
most other organisms have only been subjected to (at best)
a cursory analysis (McShea, 1996).
Human cell types 437

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ec

Fig. 1. The artificial classification scheme of cell types. The entire tabulation of 411 cell types was sorted into increasingly smaller,
more exclusive subsets based on commonly cited histological and cytological features, beginning with the cell type as a component of
one of the four basic tissue types. A total of 34 terminal groupings (assemblages) were recovered, labeled A to HH. The germ layer(s)
of origin for cell types from each assemblage are designated by symbols. See text and Appendix 1 for details. CNS, central nervous
system ; ECM, extracellular matrix ; PNS, peripheral nervous system.

(3 ) Neural crest as the fourth germ layer
With the exception of protozoans, sponges, ctenophorans,
and cnidarians, all animals have long been assumed to de-
velop from three germ layers: ectoderm, endoderm, and
mesoderm (excluding, for the moment, the role of secondary
development/neurulation). Although the term ‘layer’
seems to imply a sheet-like assemblage, in many instances
throughout development the stratified nature of these
embryonic cells is not evident. Among amniotes, including
domestic fowl, mice, and humans, cells giving rise to the
embryo proper come from the epiblast of the bilaminar
embryonic disc. Cells that migrate out of the epiblast form
the presumptive endoderm while those that remain form the
presumptive ectoderm. Mesoderm develops secondarily as
a secondary germ layer and as a result of inductive inter-
actions between presumptive ectoderm and endoderm
(Hall, 1999, 2000).
438
Fig. 2. A comparison of the cladistic and artificial classification
schemes. A cladistic analysis of eight cell types (plus one out-
group ; an undifferentiated neural crest cell) all derived from the
neural crest yields a single most parsimonious tree (tree length
of 29 steps). The artificial classification scheme from Fig. 1 was
pruned to include only those cells participating in the cladistic
analysis. A quick comparison of the two techniques demon-
strates that the results are generally not congruent, with each
method largely recovering a different pattern of cell type in-
terrelatedness. See text for details.
Recently, Hall (1998 a, b, 1999, 2000) concluded that the
neural crest also qualifies as a secondary germ layer. Similar
to mesoderm, the neural crest arises as a result of inductive
interactions. Also similar to mesoderm, neural crest cells
migrate from the neural tube to disperse throughout the
developing embryo. Hall (1998 a, b, 1999, 2000) notes that if
mesoderm is accepted as a germ layer based on the diversity
of cell types and structures that it contributes to, then the
neural crest, which also gives rise to a variety of other cell
types, should also be considered a germ layer. Indeed the
neural crest has been widely recognised as unusual among
embryonic cells. As noted by Willmer (1970, p. 136), neural
crest cells are ‘ the fly in the ointment of the classical germ-
layer theorists ’.
The notion of neural crest cells as a germ layer forms the
basis of the quadroblastic embryo, and is a feature confined
to craniates (hagfish & vertebrates) (Hall, 1999, 2000 ; see
also Shimeld & Holland, 2000). The artificial classification
scheme permits an independent test of the neural crest as a
source of cell type diversity. Of the 411 cell types considered
(including two from extraembryonic endoderm and two of
uncertain derivation), 37 are derived solely from the neural
crest and 10 are shared by both neural crest and meso-
dermally derived cells. Accordingly, neural crest cells con-
tribute to a maximum of 47 different cell types, compared
with 211 from ectoderm (including two shared with endo-
derm), 105 from mesoderm (including 10 shared with
the neural crest, and one with endoderm), and 57 from
Matthew K. Vickaryous and Brian K. Hall
(intraembryonic) endoderm (including one shared with
mesoderm and two shared with ectoderm). However, in-
cluded among the major derivatives of the neural crest are
sensory and autonomic neurons, fibroblasts, and smooth
muscle cells, all of which are immense assemblages that
remain to be fully subdivided.
Therefore, even conservative estimates demonstrate that
from a numerical standpoint, neural crest cell derivatives
are every bit as diverse as those from the classical germ
layers. Perhaps more important than quantity of resultant
cell varieties is the near ubiquitous distribution of neural-
crest-derived cell types. Unlike other germ layers, neural
crest derivatives are components of every basic tissue type
(Fig. 3). Both ectoderm and mesoderm contribute to three
basic tissue types, while endoderm is found in only one,
epithelium. The observations of Hall (1998a, b, 1999, 2000)
are fully supported, and it is unequivocally demonstrated
that the neural crest contributes to a broad diversity of cell
types associated with every major tissue type.
( 4) The evolution of cell types
As noted previously, an increase in cell type diversity is
correlated with the evolution of the neural crest germ layer.
Whereas diploblastic and triploblastic animals demonstrate
approximately 11 and 50 cell types respectively (Bonner,
1988; Carroll, 2001), quadroblastic taxa such as humans
have more than 400.
Two hypotheses have been forwarded to explain how
this increase in cell type diversity might have been
accomplished : (1) new cell types arose from undifferentiated
(embryonic germ layer) or stem cells ; or (2) existing differ-
entiated cell types developed new phenotypes via trans-
differentiation (Eisenberg & Eisenberg, 2003). In support of
the transdifferentiation hypothesis, Eisenberg & Eisenberg
(2003) noted that many invertebrates (e.g. echinoderms)
demonstrate smooth muscle cells, which are characterised as
expressing a particular set of molecules (e.g. smooth muscle
a-actin). Similarly, cardiac myocytes from avian embryos
also transiently express these smooth muscle proteins. Thus,
Eisenberg & Eisenberg (2003) theorized that cardiac myo-
cytes evolved from more primitive and ubiquitous smooth
muscle cells.
Gene expression patterns, cell behaviour, plasticity, and
morphology have also yielded evidence of ‘ protoneural crest
cells’ in non-vertebrates such as amphioxus (a cephalo-
chordate), ascidians (urochordates) and even echinoderms
(Stone & Hall, 2004). Thus, while the neural crest germ
layer is exclusive to vertebrates, precursor cells, representing
latent homologues of neural crest cells and neural crest
cell derivatives, have been identified in non-vertebrate
taxa.
In another example, the interrelationship between carti-
lage and bone cells has considerable developmental support.
Various bone markers are expressed during chondrocyte
differentiation (Eames, de la Fuente & Helms, 2003) and
hypertrophic chondrocytes demonstrate an intermediate
combination of downregulated cartilage markers and up-
regulated bone markers (Aubin et al., 1995). Furthermore,
chondrocytes are capable of transdifferentiating into
Human cell types 439

Germ (A)

Sweat (D)
Other (E)

Pituitary
Acidophilic (F)
Basophilic (G)

Protein (J)
Steroid (K)

Keratinizing (L)

Duct (O)
Hollow viscera (P)
Endothelial (Q)

Endolymphatic (S)

Blood/immune
Lymphocyte (V)
Monocyte (W)
Leukocyte (X)
Other (Y)

Skeletal
Myocyte (FF)
Spindle (GG)

Fig. 3. The artificial classification scheme of cell types derived from the neural crest. The results of Fig. 1 were pruned to reveal the
diversity of cell type assemblages that originate from the neural crest. Unlike all other germ layers the neural crest contributes to
components of every basic tissue type. See text for details. See Fig. 1 for abbreviations and Appendix 1 for label identities.

osteoblasts (Hall, 1970, 2005; Aubin et al., 1995). There also
exists an intermediate between cartilage and bone, chon-
droid bone (Mizoguchi et al., 1997 ; Hall, 2005).
Interestingly, whereas cartilage has chondrocytes and bone
has osteocytes, the cell type present in chondroid bone is
presently unclear and unnamed.
However, short of exhaustively documenting the diversity
and homologies of cell types between various craniate and
non-craniate taxa (discussed below), the most convenient
method for examining issues of cell type evolution is the
cladistic classification. For vertebrates, the neural crest
provides a particularly intriguing source of data, with con-
siderable in vitro and in vivo data.
Similar to mesodermal cells, neural crest cells demon-
strate a high degree of phenotypic plasticity, both prior to
and following differentiation (especially in vitro), which is
strongly mediated by imposed signals from the local
environment (Anderson, 1997). In other words, neural crest
440 Matthew K. Vickaryous and Brian K. Hall

(and mesodermal) cell type identity is not determined not normally considered in culture protocols. With human
intrinsically at the germ-layer stage. However, certain cells in limited supply for use in medical and biomedical
identities have a predictable distribution under non- applications (Hay, 1996), the use of cell types and cell
manipulative conditions. Fate maps of avian embryos type comparative classification schemes has the potential
demonstrate that cell type derivatives of the neural crest to offer new and alternative models for therapeutic
arise from particular regions of the rostrocaudal neural tube evaluation.
axis. For example, chondrocytes and osteocytes differentiate
from cranial neural crest cells, but not from those of the
trunk region. Using the cladistic classification scheme it is V. AREAS FOR FUTURE RESEARCH
hypothesized that, based on the most parsimonious distri-
bution of shared-derived characters, chondrocytes and
Whereas we have chosen to focus on Homo sapiens as a model
osteocytes share a close common ancestry. This notion is
taxon, the tabulation and categorisation of cell types from
independently supported by developmental evidence with
other well-known and intensively investigated taxa, includ-
numerous observations documenting progenitor cells giving
ing Mus musculus, Xenopus laevis, Danio rerio, and Drosophila
rise to either cartilage and bone cells. One such cell popu-
melanogaster, would facilitate a much needed comparative
lation occurs at the temporomandibular joint in humans
evolutionary approach. However, just as for previous esti-
and mice where it gives rise to the condylar cartilage and
mates of human cell type diversity, tabulations for most of
osseous tip of the condylar process (Baume, 1962 ; Hall,
these taxa are incomplete. A histological investigation of
1970, 2005).
the optic lobe of wild-type Drosophila melanogaster (Fischbach
Another example is the relationship between chromaffin
& Dittrich, 1989) found more than 100 different types of
cells, parafollicular (C) cells, and sympathetic neurons, all of
neurons, compared with some estimates suggesting only
which are considered by the cladistic classification scheme
50 to 90 cell types for the entire organism (Bonner, 1988 ;
as a unified group (the clade of biogenic amine-handling
Valentine, 2003). Clearly, this remains an important topic
cells). In sheep, both parafollicular and chromaffin cells
for further investigation.
demonstrate a variety of neural properties in culture and,
As discussed, the use of DNA microarrays has an obvious
along with sympathetic neurons, are responsive to b-nerve
future role in defining and discriminating cell types.
growth factor (Barasch et al., 1987). Whereas parafollicular
However, this should not be interpreted as justification for
cells closely resemble neurons (to the point of being called
abandoning more traditional phenotypic characterisations ;
paraneurons), other evidence suggests that chromaffin
molecular data do not replace cytology and histology. As
cells share a common progenitor with sympathetic neurons
eloquently demonstrated by Toledo-Rodriguez et al. (2005)
(Barasch et al., 1987). Furthermore, in rats, sympathoadrenal
for juvenile rat neurons, the same cell types identified
progenitor cells in culture produce either chromaffin cells
by gene expression data are also recovered using more
or sympathetic neurons, but are unable to differentiate
traditional morphologically based diagnostic methods.
into glia cells, sensory neurons, or melanocytes (Anderson,
Thus, the two techniques not only corroborate each
1997).
another, but enhance the data set. What is currently needed
In humans, the results of the cladistic classification
is greater emphasis on reintegrating the intimately related
scheme also receive support from the study of cell lines
and yet increasingly divorced subdisciplines of histology
established in culture from neuroblastomas, an early child-
and molecular biology.
hood cancer arising from the neural crest. These cell lines
In addition to the aforementioned phenotypic-gene
include N (neuroblastic) cells, small and rounded with
expression assimilation, various other sources of data are
neurite-like processes, and S (substrate-adherent) cells,
also worth exploring. For instance, many cell types share
larger, flattened and fibroblast-like (Ciccarone et al., 1989).
(at least in part) differentiation pathways and in doing so
Whereas the N cells have been likened to noradrenergic
express the same specific transcription factors during
neurons, the S cells more closely resemble melanocytes.
development – e.g. among haematopoetic cells, both
Each of these cell types is derived from a common pre-
megakaryocytes and erythrocytes arise from a common
cursor, and each may spontaneously transdifferentiate
multipotential progenitor cell and share the zinc finger
into the other (Ciccarone et al., 1989), consistent with the
transcription factor GATA1 (Romeo et al., 1990; Auron,
proximate position of these cell types to one another within
2005). Similarly, some closely related cell types may actively
the cladogram.
suppress one another, as in mice where motorneurons
Perhaps not surprisingly, these results demonstrate a
can curb the differentiation of interneurons (Thaler et al.,
strong (albeit independently derived) correlation between
1999). Additional data may be gleaned from common
cell type evolution (as proposed by the cladistic analysis) and
inherited epigenetic factors, such as specific patterns of
development (as evidenced by in vitro studies). Ultimately this
DNA methylation.
relationship may prove to be useful in a clinical context.
From a practical standpoint, knowledge of cell type diversity
and evolution may offer a theoretical means of prediction
for the fields of medicine, biochemistry, and pharmacology. VI. CONCLUSIONS
With continued refinement of the cell type list and classifi-
cation scheme it may become possible to explore, by infer- (1) Cell types are mutable biological units, comparable
ence, reactions to drugs and chemical agents on cell types with species and genes. As such, most definitions are
Human cell types
awkward, problematic, and incomplete. In the simplest
sense, all members of a particular cell type must demon-
strate at least one unique feature and/or share some
combination of characteristics that is/are unlike the unique
feature or combination of characteristics found in other cell
types. Members of the cell type are more similar to each
other than they are to non-member cells.
(2) As a matter of convenience, and functional and
comparative utility, cell types need to be organised into
groupings. Given the parallels between cell types and
species, we investigated two categorisation methods em-
ployed by biological systematists : artificial (key) and cladistic
classification.
(3) Cell type diversity is achieved via several different
pathways, including gastrulation and transdifferentiation,
from a blastema, and from stem cells. As all cells derived
from the same zygote have the same genome (at least
initially), the amounts and pattern of gene expression and
epigenetic mechanisms guide the differentiation of the
various cell types.
(4) Humans are a logical and self-serving model to
explore cell type diversity and classification. Expertise on
human cell types is widespread in both biological and clini-
cal sciences (e.g. among histologists, pathologists, cancer
researchers, and developmental geneticists to name a few),
providing us with at least a rudimentary understanding of
normal and abnormal developmental patterns.
(5) In humans, the number of cell types present in the
adult is revised to 411, including 145 types of neurons.
(6) An artificial classification scheme was constructed
based on commonly cited cytological, histological, and func-
tional criteria, resulting in 34 terminal categories, including
support connective tissues, lymphocytes, and central
nervous system neurons. Mapping the germ layer of origin
onto the artificial scheme provides support for the notion of
the neural crest as the fourth germ layer. Significantly, the
neural crest is unique among germ layers in providing
cellular contributions to each of the four traditional tissue
types : epithelial, connective, nervous, and muscular.
(7) As an alternative, we provide an example of a
cladistic analysis wherein a representative subset of neural-
crest-derived cell types is categorised using shared derived
characteristics. This method has the advantage that the
resulting hypotheses are testable and repeatable. Signifi-
cantly, the results of the cladistic analysis are corrob-
orated by in vitro developmental studies. Future cladistic
investigations of cell types have numerous sources of data
to draw upon, including gene expression profiles, shared
transcription factors, and common epigenetic mechanisms.
VII. ACKNOWLEDGEMENTS
This work stems from a stimulating series of discussions the first
author had with Dr P. Neumann (Dalhousie) and his input is
gratefully acknowledged. Significant improvements to the text
were the result of comments by two anonymous reviewers. Other
helpful comments were provided by Dr J. R. Stone (McMaster
University, Hamilton) and T. Edwards (Dalhousie). This work was
supported by an NSERC operating grant to B. K. H.
441
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444 Matthew K. Vickaryous and Brian K. Hall

Appendix 1. Catalogue of 411 Homo sapiens cell types. Alphabetical assemblage designation refers to the terminal categories of the
artificial classification scheme (Fig. 1). The symbolpindicates a more exclusive subdivision of the preceeding category. Organs and
other anatomical entities listed under notes are offset by square brackets. List of abbreviations : CCK, cholecystokinin ; CNS,
central nervous system ; ct, connective tissue ; ECM, extracellular matrix ; endo, endoderm ; ecto, ectoderm ; ep, epithelial tissue ;
extra endo, extraembryonic endoderm ; GABAergic, gamma-aminobutyric acidergic ; meso, mesoderm ; mm, muscular tissue ;
ncrt, neural crest ; ns, nervous tissue ; PNS, peripheral nervous system ; VIP, vasoactive intestinal peptide ; ?, germ layer of origin
remains uncertain. Primary sources of information : Alberts et al. (1989) ; Anderson (1989) ; Canning & Fischer (2001) ; Campbell
et al. (1989) ; Cant & Benson (2003) ; Caterina & Julius (1999) ; Dacey (1994) ; Lentz (1971) ; Kieranan (1998) ; Kolb et al. (1992) ;
Matthews (1989) ; Mugnaini & Floris (1994) ; Ostapoff et al. (1994) ; Sanders et al. (1999) ; Somogyi & Klausberger (2005) ; Solcia et al.
(1987) ; Yáňez et al. (2005) ;Yelnik et al. (1991). See text for details

Assem- Germ Traditional

blage Cell type layer tissue type Notes

epitheliumpgerm
A oocyte extra endo ? spermatozoa are usually referred to as epithelial
A spermatozoa extra endo ep based on how they develop within the
seminiferous tubules and, by default, some
authors also characterise oocytes in a similar
fashion leading to difficulties in categorising
follicular cells
epitheliumpsomaticpglandpexocrinepmucous
B epithelial mucous membrane cell endo ep merocrine gland ; product secreted by exocytosis
[respiratory tract]
B gland cell, Bartholin’s meso ep merocrine gland ; vaginal lubricant [female
reproductive tract]
B gland cell, Brunner’s endo ep merocrine gland ; alkaline solution of mucous
and enzymes [duodenum]
B gland cell, bulbourethral endo ep merocrine gland ; mucous [male reproductive
tract]
B gland cell, Littré meso ep merocrine gland ; mucous
B gland cell, salivary, mucous ecto ep merocrine gland
B goblet cell endo ep merocrine gland ; mucous [respiratory, digestive
tracts]
B secretory stomach cell endo ep merocrine gland ; mucous
epitheliumpsomaticpglandpexocrinepprotein secreting
C acinar cell endo ep merocrine gland [pancreas]
C gland cell, Bowman’s dark ecto ep merocrine gland
C gland cell, Bowman’s light ecto ep merocrine gland
C gland cell, lacrimal ecto ep merocrine gland ; tears
C gland cell, salivary, serous ecto ep merocrine gland
C gland cell, von Ebner’s ecto ep merocrine gland ; secretion to wash over taste
buds [tongue]
C Paneth cell endo ep merocrine gland [small and large intestines]
C pneumocyte, type II, great alveolar cell endo ep merocrine gland
(septal cell)
C secretory fallopian tube cell meso ep merocrine gland
C zymogenic cell endo ep merocrine gland ; secreting pepsinogen
epitheliumpsomaticpglandpexocrinepsweat
D gland cell, ceruminous ecto ep modified sweat gland ; wax
D gland cell, mammary ecto ep modified sweat gland
D gland cell, Moll ecto ep modified sweat gland [eyelid]
D gland cell, sweat, apocrine ecto ep apocrine gland ; odoriferous secretion, sex
hormone sensitive
D gland cell, sweat, eccrine clear ecto ep clear secretion
D gland cell, sweat, eccrine dark ecto ep dark secretion
epitheliumpsomaticpglandpexocrinepother
E gland cell, prostate endo ep merocrine gland ; components of seminal fluid
E hepatocyte endo ep merocrine gland
E oxyntic (parietal) cell endo ep merocrine gland [stomach]
E sebaceous gland cell ecto ep holocrine cell ; lipid-rich sebum
E secretory endometrial cell meso ep merocrine gland ; secreting mainly carbohydrates
E secretory seminal vesicle cell meso ep merocrine gland
Human cell types 445

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

epitheliumpsomaticpglandpendocrineppituitarypacidophilic
F pituitary cell, anterior, growth hormone ecto ep somatotrophe
secreting
F pituitary cell, anterior, prolactin secreting ecto ep mammotrophe
epitheliumpsomaticpglandpendocrineppituitarypbasophilic
G pituitary cell, anterior, adrenocortico- ecto ep corticotrophe
trophic secreting
G pituitary cell, anterior, thyroid- ecto ep thyrotrope
stimulating hormone secreting
G pituitary cell, follicle stimulating ecto ep gonadotroph
hormone secreting
G pituitary cell, intermediate, melanocyte ecto ep corticotrophe
stimulating hormone secreting
G pituitary cell, luteinizing hormone ecto ep gonadotroph
secreting
epitheliumpsomaticpglandpendocrinepnon-pituitarypamino acid
H argentaffin cell endo ep enterochromaffin [EC] cell, secreting serotonin
[stomach, small and large intestines]
H chromaffin cell, epinephrine secreting ncrt ?ns [adrenal gland]
H chromaffin cell, norepinephrine secreting ncrt ?ns [adrenal gland]
H pinealocyte ecto ?ns secreting melatonin
H small intensely fluorescent (SIF) cell, ncrt ?ns interneuron-like form ; synthesise and store
type I catecholamines
H small intensely fluorescent (SIF) cell, ncrt ?ns endocrine-like form ; synthesise and store
type II catecholamines
H thyroid follicular cell endo ep thyroid hormone secreting
epitheliumpsomaticpglandpendocrinepnon-pituitaryppeptide
I alpha cell endo ep [islet of Langerhans]
I carotid body type I cell ncrt ?ct the carotid body contains various peptides
(enkephalin, neurotensin, bombesin), with
smaller amounts of amines (norepinephrine and
epinephrine) (Stevens & Lowe, 1997)
I chromophobic (C) cell endo ep [islet of Langerhans]
I delta cell endo ep secrete somatostatin [islet of Langerhans,
respiratory and digestive tracts]
I gastroenteropancreatic CCK secreting endo ep also called I cell [small intestine]
cell
I gastroenteropancreatic en- endo ep unknown product, ?serotonin [stomach]
terochromaffin-like (ECL) cell
I gastroenteropancreatic endocrine cell, endo ep [stomach, small intestine]
P cell
I gastroenteropancreatic gastrin secreting endo ep [stomach]
(G) cell
I gastroenteropancreatic glucagon endo ep [pancreas]
secreting (A) cell
I gastroenteropancreatic glucagon- endo ep also called K cell [small intestine]
dependent insulinotropic peptide
secreting (GIP) cell
I gastroenteropancreatic glucagon-like endo ep also called L cell [small and large intestines]
peptide-2 secreting (GLP-2) cell
I gastroenteropancreatic motilin secreting endo ep [small intestine]
(M) cell
I gastroenteropancreatic neurotensin endo ep [small intestine]
secreting (N) cell
I gastroenteropancreatic pancreatic endo ep [pancreas]
polypeptide secreting (PP) cell
I gastroenteropancreatic peptide tyrosine endo ep also called L cell [small and large intestines]
tyrosine secreting (PYY) cell
I gastroenteropancreatic secretin secreting endo ep [small intestine]
(S) cell
446 Matthew K. Vickaryous and Brian K. Hall

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

I gastroenteropancreatic gastrin/CCK endo ep also called TG cell ; main products are C-terminal
secreting cell gastrin and CCK [small intestine]
I gastroenteropancreatic very large (VL) endo ep unknown product [small intestine]
cell
I gastroenteropancreatic X cell endo ep unknown product [stomach]
I Hassall’s (thymic) corpuscle epithelial endo ep epithelial cells that become embedded within the
cell thymus ; granules contain keratohyalin
I parafollicular (C) cell ncrt ep secrete calcitonin [thyroid]
I pineal interstitial cell ecto ?ns secrete luteinizing hormone
I principal (chief ) cell endo ep [parathyroid]
I pulmonary (P) endocrine cell, bombesin endo ep [respiratory tract]
I secretory cell, endorphin ? ?ep [gut and respiratory tract]
I secretory cell, oxytocin ecto ?ep, ns [hypothalamus]
I secretory cell, vasopression ecto ?ep, ns [hypothalamus]
I Sertoli cell meso ep Sertoli cells are polyfunctional ; they secrete
inhibitin, support the developing spermatozoa and
phagocytose residual bodies (Stevens & Lowe,
1997)
I testis interstitial cell meso ct
I thymic epithelial-reticular (TER) cell endo ep [thymus]
epitheliumpsomaticpglandpendocrinepnon-pituitarypprotein
J beta cell endo ep insulin secreting [islet of Langerhans, respiratory
and digestive tracts]
J gland cell, parathyroid endo ep parathyroid hormone
J peripolar cell meso ep granulated epithelial cell localized at the vascular
pole of the glomerulus ; granules contain albumin,
immunoglobulins, and neuron-specific enolase
J secretory cell, renin meso ep renin secreting cells regulate blood pressure ;
appear to represent precursors for various other
cell types (including smooth muscle and epithelial
cells) that dedifferentiate in response to stress
(López, et al., 2004) [juxtaglomerular apparatus,
kidney]
epitheliumpsomaticpglandpendocrinepnon-pituitarypsteroid
K corpus luteum cell meso ep progesterone secreting [ruptured ovarian follicle]
K follicle cell meso ct estradiol [ovary]
K Leydig cell meso ep Interstitial cell ; secretes androgens in foetus [testis]
K theca interna cell meso ep or ct ? estrogen secreting [ovarian follicle]
K zona fasciculata and reticularis cell, meso ep steroid hormones, glucocorticoids [adrenal gland]
glucocorticoid secreting
K zona fasciculata and reticularis cell, meso ep steroid hormones, mineralocorticoids secreting
mineralocorticoid secreting [adrenal gland]
K zona fasciculata cell meso ep relatively large, foamy-looking, cortisol secreting
cells [adrenal gland]
K zona glomerulosa cell meso ep relatively small cells that cluster in groups ;
steroid hormones and mineralocorticoids
secreting [adrenal gland]
K zona reticularis cell meso ep cells arranged as interconnecting cords ;
androstenedione [adrenal gland]
epitheliumpsomaticpsurface epitheliumpcoveringpkeratinizing
L hair cell, cortical ecto ep
L hair cell, cuticular ecto ep
L hair cell, cuticular, root ecto ep [hair root]
L hair cell, external ecto ep [hair root]
L hair cell, Henle’s layer ecto ep [hair root]
L hair cell, Huxley’s layer ecto ep [hair root]
L hair cell, medullary ecto ep
L hair cell, shaft ecto ep
L hair cell, sheath ecto ep [hair root]
L keratinocyte ecto ep [epidermis, fingernails, toenails]
Human cell types 447

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

epitheliumpsomaticpsurface epitheliumpcoveringpnon-keratinizing
M epithelial cell, anterior lens ecto ep
M epithelial cell, conjunctival ecto ep
M lens fibre cell ecto ep crystallin containing
M melanocyte ncrt ?ep
epitheliumpsomaticpsurface epitheliumpliningpserosal cell
N mesothelial cell meso ep
N serosal cell meso ep [lining peritoneal, pleural and pericardial cavities]
N synovial A cell meso, ncrt ct phagocytic with numerous lysosomes
N synovial B cell meso, ncrt ct abundant rough endoplasmic reticulum ; produce
synovial fluid
epitheliumpsomaticpsurface epitheliumpliningpducts
O brush border cell meso ep [proximal tubule of kidney]
O centroacinar cells endo ep also called duct cell [pancreas]
O ciliated female reproductive cell meso ep [oviduct and uterus]
O ciliated male reproductive cell meso ep [ductuli efferentes]
O ciliated respiratory tract cell endo ep
O duct cell, bile duct endo ep
O duct cell, collecting tubule meso ep [kidney]
O duct cell, ductus epididymidis meso ep [epithelium]
O duct cell, gall bladder endo ep
O duct cell, intercalated, salivary gland ecto ep
O duct cell, nonstriated ecto ep present in sweat, salivary, and mammary glands
O duct cell, seminal vesicle and prostate meso ep
gland
O duct cell, striated, salivary gland ecto ep
O epithelial cell, distal tubule meso ep [kidney]
O epithelial cell, prostatic endo ep
O epithelial cell, proximal tubule meso ep [kidney]
O epithelial cell, thick loop of Henle meso ep [kidney]
O epithelial cell, thin limb loop of Henle meso ep [kidney]
O epithelial cell, transitional endo ep
O epithelial cell, urinary system endo ep
O macula densa cell, distal tubule meso ep cells packed into a zone of the distal tubule ad-
jacent to the glomerulus ; may function as a sensor
monitoring Na+ and Clx levels (Stevens & Lowe,
1997)
O non-ciliated cell, ductuli efferentes meso ep
O parietal cell, kidney glomerulus meso ep
O podocyte, glomerular epithelial cell ?endo, meso ep
O principal cell, epididymis meso ep
epitheliumpsomaticpsurface epitheliumpliningphollow viscera
P brush border cell, intestine (with endo ep
microvilli)
P Clara cell endo ep neither ciliated nor mucous producing ; function
unknown [lung]
P epithelial cell, stratified squamous endo, ecto ep may arise from either ectoderm or endoderm and
may represent undocumented diversity of cell
types [tongue, oral cavity, esophagus, anal canal,
distal urethra, vagina]
P epithelial cell, stratified squamous ncrt ep [cornea]
corneal
P epithelial cell, intestinal endo ep
P epithelial cell, lung (pulmonary) endo ep
P epithelial cell, olfactory, olfactory cell ecto ep
P epithelial cell, olfactory, supporting ecto ep
P epithelial cell, olfactory, sustentacular ecto ep
cell
P epithelial cell, respiratory, basal cell endo ep
P epithelial cell, respiratory, brush cell endo ep
448 Matthew K. Vickaryous and Brian K. Hall

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

P epithelial cell, respiratory, ciliated cell endo ep

P pneumocyte, type I endo ep flattened cells lining the airways
P type I taste bud cell ecto ep taste bud supporting cell
P type II taste bud cell endo, ecto ep experiments by Stone et al. (1995) demonstrate that
taste bud cells can arise from either ectoderm or
endoderm and share a common progenitor with
local oral epithelial cells ; taste bud cells are not
neurogenic ectoderm
epitheliumpsomaticpsurface epitheliumpliningpendothelial cell
Q endothelial cell, continuous meso ct
Q endothelial cell, CNS meso ct
Q endothelial cell, fenestrated meso ct
Q endothelial cell, lymphatic meso ct
Q endothelial cell, corneal meso ep
Q endothelial cell, splenic meso ep
Q littorial cell meso ct
epitheliumpsomaticpsurface epitheliumpliningpCNS derivative
R carotid body type II cell ? ?
R choroid plexus cell ecto ep secreting cerebrospinal fluid
R ciliary pigmented epithelial cell ecto ep [eye]
R ciliary unpigmented epithelial cell ecto ep [eye]
R ependymal cell ecto ?ep, ns
R Merkel cell, epidermis ecto ?ns sensory receptors of the epidermis ; contain
neuroendocrine vesiscles ; neuroepithelium
R myoepithelial cell, iris ncrt ?ep contractile cells
R neuron, mitral cell ecto ns second order neurons contacted by olfactory
neurons [olfactory bulb]
R neuron, olfactory ecto ns olfactory neuroepithelium
R neuron, olfactory bulb granule cell ecto ns interneuron [olfactory bulb]
R neuron, periglomerular cell ecto ns olfactory interneuron [olfactory bulb]
R neuron, tufted cell ecto ns second order neurons contacted by olfactory
neurons
R pigment epithelial cell, retina ecto ep
R squamous cell, pia-arachnoid ncrt ep
R tanycytes ecto ?ep, ns ependyma cells with long basal processes
epitheliumpsomaticpsurface epitheliumpliningpendolymphatic cells
S Boettcher cell ecto ep [organ of Corti]
S Claudis cell ecto ep [organ of Corti]
S columnar cell with microvilli ecto ep [endolymphatic sac]
S columnar cell without microvilli ecto ep [endolymphatic sac]
S dark cell, crista ampullaris ecto ep [vestibular apparatus]
S dark cell, endolymphatic sac ecto ep [vestibular apparatus]
S hair cell, organ of Corti, inner ecto ep
S hair cell, organ of Corti, outer ecto ep
S hair cell, type I ecto ep [vestibular apparatus]
S hair cell, type II ecto ep [vestibular apparatus]
S light cell ecto ep [endolymphatic sac, vestibular apparatus]
S vestibular apparatus membrane cell ecto ep
S phalangeal cell, inner supporting ecto ep [organ of Corti]
S phalangeal cell, outer supporting ecto ep [organ of Corti]
S pillar cell, inner supporting ecto ep [organ of Corti]
S pillar cell, outer supporting ecto ep [organ of Corti]
S squamous cell, endolymphatic sac lining ecto ep
S squamous cell, perilymphatic space ecto ep
lining
S stellate cell, perilymphatic space lining ecto ep
S stria vascularis basal cell ecto ep [cochlea]
S stria vascularis intermediate cell ecto ep [cochlea]
S stria vascularis marginal cell ecto ep [cochlea]
S supporting border cell ecto ep [organ of Corti]
Human cell types 449

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

S supporting cell, organ of Corti ecto ep

S supporting cell, vestibular apparatus ecto ep
connective tissuepsupportpstorage
T adipose cell, brown meso ct
T adipose cell, lipocyte of liver meso ct
T adipose cell, white meso, ncrt ct
connective tissuepsupportpECM secreting
U cementoblast meso ct secrete cementum
U chondrocyte, elastic cartilage meso, ncrt ct
U chondrocyte, fibrocartilage meso, ncrt ct
U chondrocyte, hyaline cartilage meso, ncrt ct
U fibroblast meso, ncrt ct may represent an undocumented diversity of
cell types (Fries et al., 1994) ; may also include
myofibroblasts
U fibroblastic reticular cell meso ct
U hyalocyte, vitreous body of eye ecto ct
U interdental cell ecto ep secrete tectorial ‘membrane ’ covering hair cells
of organ of Corti
U mesangial cell meso mm
U nucleus pulposus cell meso ct fomerly notochord [intervertebral disc]
U odontoblast ncrt ct
U osteocyte meso, ncrt ct
U pericyte, blood capillary meso, ncrt mm spindle-shaped, putatively contractile cells ;
assume role of mesenchyme following injury and
differentiate into myofibroblasts and new blood
vessels (Stevens & Lowe, 1997) ; considered by
some to be a non-skeletal muscle cell (category
HH)
U planum semilunatum cell ecto ep secrete proteoglycan [vestibular apparatus]
U tenocyte meso ct connective tissue cell of tendons
connective tissuepblood/immuneplymphocytes
V lymphocyte, helper T meso ct
V lymphocyte, IgA B meso ct
V lymphocyte, IgE B meso ct
V lymphocyte, IgG B meso ct
V lymphocyte, IgM B meso ct
V lymphocyte, killer cell meso ct
V lymphocyte, killer T meso ct
V lymphocyte, suppressor T meso ct
V plasma cell meso ep
V thymocyte endo ct
connective tissuepblood/immunepmonocyte
W chondroclast meso ct
W dendritic cell meso ct [in lymphoid tissue]
W Kupffer cell meso ct [liver]
W Langerhans cell, epidermis meso ct
W macrophage, alveolar meso ct [lung]
W macrophage, connective tissue meso ct sometimes referred to as a histiocyte
W macrophage, multinucleated meso ct
W macrophage, serous cavity meso ct
W macrophage, splenic meso ct [spleen]
W microglia meso ns [central nervous system]
W monocyte meso ct
W mononucleated osteoclast meso ct some argue that osteoclasts may arise from
monocytes and/or macrophages (see Hall, 2005)
W multinucleated osteoclast meso ct
W pituitary folliculo-stellate cell ecto ct non-endocrine, ‘excitable ’ cell
W plasmacytoid dendritic cell meso ct produces interferons in response to viruses ; also
called plasmacytoid monotcytes and interferon
producing cells
450 Matthew K. Vickaryous and Brian K. Hall

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

connective tissuepblood/immunepleukocyte
X leukocyte, basophil meso ct
X leukocyte, eosinophil meso ct
X leukocyte, globule meso ct
X leukocyte, granulocyte meso ct endometrial
X leukocyte, neutrophils meso ct
X mast cell meso ct
connective tissuepblood/immunepother
Y erythrocyte meso ct
Y megakaryocyte meso ct
nervous tissuepgliapPNS
Z enteric (astrocyte-like) glial cell ncrt ns
Z pituicyte ecto ?ns pituitary cell
Z satellite cell ncrt ns encapsulating nerve cell bodies [PNS]
Z Schwann cell ncrt ns
nervous tissuepgliapCNSpastrocytes
AA astrocyte, fibrous ecto ns
AA astrocyte, protoplasmic (velate) ecto ns
AA Muller cell ecto ns retinal support cells
nervous tissuepgliapCNSpoligodendrocytes
BB oligodendrocyte, interfascicular ecto ns
BB oligodendrocyte, Satellite ecto ns
nervous tissuepneuronpPNS
CC neuron, enteric, interneuron ncrt ns secrete serotonin
CC neuron, enteric, motor to ncrt ns
gastroenteropancreatic endocrine cell
CC neuron, enteric, motor, excitatory ncrt ns
CC neuron, enteric, motor, inhibitory ncrt ns
CC neuron, enteric, secretomotor/ ncrt ns
vasomotor
CC neuron, enteric, sensory ncrt ns
CC neuron, enteric, stubby ncrt ns
CC neuron, motor, A-alpha (IA) ecto ns myelinated ; proprioception [muscle spindle]
CC neuron, motor, A-gamma ecto ns myelinated ; motor to intrafusal fibres to muscle
spindles
CC neuron, parasympathetic, cholinergic ncrt ns
CC neuron, parasympathetic, non- ncrt ns [respiratory system and smooth muscle
adrenergic/non-cholinergic (NANC) innervation]
CC neuron, sensory, A-beta IB ncrt ns myelinated ; tonic proprioception ;
mechanoreception
CC neuron, sensory, A-beta IIB ncrt ns myelinated ; tendon proprioception
CC neuron, sensory, A-delta cold fibre ncrt ns thermoreceptor ; sensitive to cooling
CC neuron, sensory, A-delta type I ncrt ns nociceptor/mechano-thermoreceptor ;
hyperalgesic pain
CC neuron, sensory, A-delta type II ncrt ns nociceptor/mechano-thermoreceptor ; pricking
(first) pain
CC neuron, sensory, C-fibre non-peptidergic ncrt ns unmyelinated ; burning pain ; nociceptor,
mechano-thermoreceptor
CC neuron, sensory, C-fibre peptidergic ncrt ns unmyelinated ; burning pain ; nociceptor,
mechano-thermoreceptor
CC neuron, sensory, mechanoreceptor, other ncrt ns
CC neuron, sensory, proprioceptor, other ncrt ns
CC neuron, sensory, warm fibre ncrt ns thermoreceptor ; sensitive to gentle warming
CC neuron, sympathetic, adrenergic ncrt ns also present in special (visual) sensory component
of the CNS (category DD)
CC neuron, sympathetic, B-fibre ncrt ns myelinated ; preganglionic
CC neuron, sympathetic, C-fibre ncrt ns unmyelinated ; postganglionic
CC neuron, sympathetic, cholinergic ncrt ns also present in special (visual) sensory component
of the CNS (category DD)
Human cell types 451

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

nervous tissuepneuronpCNSpspecial (visual) sensory

DD cone photoreceptors, blue sensitive ecto ns
DD cone photoreceptors, green sensitive ecto ns
DD cone photoreceptors, red sensitive ecto ns
DD neuron, amacrine cholinergic stratum 2 ecto ns medium-field amacrine cell [retina]
DD neuron, amacrine cholinergic stratum 4 ecto ns medium-field amacrine cell [retina]
DD neuron, amacrine semilunar type 1 ecto ns large-field amacrine cell [retina]
DD neuron, amacrine semilunar type 2 ecto ns large-field amacrine cell [retina]
DD neuron, amacrine small-field diffuse ecto ns small-field amacrine cell [retina]
DD neuron, amacrine spiny ecto ns medium-field amacrine cell [retina]
DD neuron, amacrine stellate-varicose ecto ns large-field amacrine cell [retina]
DD neuron, amacrine thorny type 1 ecto ns large-field amacrine cell [retina]
DD neuron, amacrine thorny type 2 ecto ns large-field amacrine cell [retina]
DD neuron, amacrine tristratified ecto ns medium-field amacrine cell [retina]
DD neuron, amacrine type A1 ecto ns small-field amacrine cell [retina]
DD neuron, amacrine type A2 ecto ns small-field amacrine cell [retina]
DD neuron, amacrine type A3 ecto ns small-field amacrine cell [retina]
DD neuron, amacrine type A4 ecto ns small-field amacrine cell [retina]
DD neuron, amacrine type A5 ecto ns small-field amacrine cell [retina]
DD neuron, amacrine type A8 ecto ns small-field amacrine cell [retina]
DD neuron, amacrine type A12 ecto ns medium-field amacrine cell [retina]
DD neuron, amacrine type A13 ecto ns medium-field amacrine cell [retina]
DD neuron, amacrine type A14 ecto ns medium-field amacrine cell [retina]
DD neuron, amacrine type A17 spidery- ecto ns large-field amacrine cell [retina]
diffuse
DD neuron, amacrine type A18 ecto ns large-field amacrine cell [retina]
DD neuron, amacrine type AII ecto ns small-field amacrine cell [retina]
DD neuron, amacrine wavy ecto ns large-field amacrine cell [retina]
DD neuron, amacrine wiry ecto ns large-field amacrine cell [retina]
DD neuron, amacrine wooly diffuse ecto ns medium-field amacrine cell [retina]
DD neuron, bistratified giant bipolar ecto ns [retina]
DD neuron, blue cone bipolar cell type a ecto ns axon terminal branches in sublamina a [retina]
(Kolb et al., 1992)
DD neuron, blue cone bipolar cell type b ecto ns axon terminal branches in sublamina b [retina]
(Kolb et al., 1992)
DD neuron, diffuse cone bipolar cell type a ecto ns axon terminal branches in sublamina a [retina]
(Kolb et al., 1992)
DD neuron, diffuse cone bipolar cell type b ecto ns axon terminal branches in sublamina b [retina]
(Kolb et al., 1992)
DD neuron, flat midget bipolar ecto ns [retina]
DD neuron, ganglion G3 ecto ns [retina]
DD neuron, ganglion G4 ecto ns [retina]
DD neuron, ganglion G5 ecto ns [retina]
DD neuron, ganglion G7 ecto ns [retina]
DD neuron, ganglion G8 ecto ns [retina]
DD neuron, ganglion G10 ecto ns [retina]
DD neuron, ganglion G11 ecto ns [retina]
DD neuron, ganglion G12 ecto ns [retina]
DD neuron, ganglion G16 ecto ns [retina]
DD neuron, ganglion G17 ecto ns [retina]
DD neuron, ganglion G19 ecto ns [retina]
DD neuron, ganglion G20 ecto ns [retina]
DD neuron, ganglion G21 ecto ns [retina]
DD neuron, ganglion G22 ecto ns [retina]
DD neuron, ganglion G23 ecto ns [retina]
DD neuron, ganglion M ecto ns also called parasol or giant parasol ganglion cell
[retina]
DD neuron, ganglion P1 ecto ns also called midget ganglion cell [retina]
DD neuron, ganglion P2 ecto ns also called shrub or small parasol ganglion cell
[retina]
452 Matthew K. Vickaryous and Brian K. Hall

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

DD neuron, giant diffuse bipolar ecto ns [retina]

DD neuron, horizontal type HI ecto ns [retina]
DD neuron, horizontal type HII ecto ns [retina]
DD neuron, horizontal type HIII ecto ns [retina]
DD neuron, interplexiform ecto ns [retina]
DD neuron, invaginating midget bipolar ecto ns [retina]
DD neuron, rod bipolar cell ecto ns [retina]
DD neuron, sympathetic, adrenergic ncrt ns also present in the PNS (category CC)
DD neuron, sympathetic, cholinergic ncrt ns also present in the PNS (category CC)
DD rod cell ecto ns [retina]
nervous tissuepneuronpCNSpother
EE neuron, antenniform cell ecto ns [cochlear nuclei, medulla oblongata]
EE neuron, axo-axonic ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, back-projection ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, basket cell type I ecto ns non-pyramidal, GABAergic (interneuron),
parvalbum positive, CCK negative [cerebral
cortex]
EE neuron, basket cell type II ecto ns non-pyramidal, GABAergic (interneuron),
parvalbum negative, CCK positive, VIP positive
[cerebral cortex]
EE neuron, basket cell type III ecto ns non-pyramidal, GABAergic (interneuron),
parvalbum negative, CCK positive, VIP negative
[cerebral cortex]
EE neuron, Betz cell ecto ns [cerebral cortex]
EE neuron, bilaminar ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, bistratified ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, CA1 oriens alveus interneuron ecto ns [hippocampus]
EE neuron, CA1 pyramidal ecto ns [hippocampus]
EE neuron, CA3 pyramidal ecto ns [hippocampus]
EE neuron, cell of Martinotti ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, chandelier ecto ns [cerebral cortex]
EE neuron, clavate cell ecto ns [cochlear nuclei, medulla oblongata]
EE neuron, dentate granule cell ecto ns [dentate region of archicortex]
EE neuron, double bouquet cell (DBC) ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, elongate cell ecto ns [cochlear nuclei, medulla oblongata]
EE neuron, fusiform cell ecto ns [cerebral cortex]
EE neuron, giant cell ecto ns [cochlear nuclei, medulla oblongata]
EE neuron, globular bushy cell ecto ns [cochlear nuclei, medulla oblongata]
EE neuron, Golgi cell ecto ns [cerebellar cortex]
EE neuron, granule cell ecto ns [cerebellar cortex, olfactory bulb, hippocampus]
EE neuron, hippocampal-septal ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, interneurone specific cell I (IS-I) ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, interneurone specific cell II ecto ns non-pyramidal, GABAergic (interneuron)
(IS-II) [cerebral cortex]
EE neuron, interneurone specific cell III ecto ns non-pyramidal, GABAergic (interneuron)
(IS-III) [cerebral cortex]
EE neuron, lacunosaum-moleculare ecto ns non-pyramidal, GABAergic (interneuron)
perforant path associated [cerebral cortex]
EE neuron, lacunosaum-moleculare- ecto ns non-pyramidal, GABAergic (interneuron)
radiatum perforant path associated [cerebral cortex]
EE neuron, large spherical bushy cell ecto ns [cochlear nuclei, medulla oblongata]
EE neuron, neostriatal cholinergic ecto ns [neostratum]
interneuron
Human cell types 453

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

EE neuron, neurogliaform cell ecto ns non-pyramidal cell, GABAergic (interneuron)

[cerebral cortex]
EE neuron, nigral dopaminergic cell ecto ns [substantia nigra]
EE neuron, octopus cell ecto ns
EE neuron, olfactory cortex interneuron ecto ns [olfactory cortex]
(deep)
EE neuron, olfactory cortex interneuron ecto ns [olfactory cortex]
(superficial)
EE neuron, olfactory cortex pyramidal cell ecto ns [olfactory cortex]
EE neuron, Purkinje cell ecto ns [cerebellar cortex]
EE neuron, pyramidal cell ecto ns [cerebral cortex]
EE neuron, Renshaw cell ecto ns interneuron [spinal cord]
EE neuron, Retzius-Cajal cell ecto ns [cerebral cortex]
EE neuron, Schaffer collateral associated ecto ns non-pyramidal, GABAergic (interneuron)
[cerebral cortex]
EE neuron, small spherical bushy cell ecto ns [cochlear nuclei, medulla oblongata]
EE neuron, spinal Ia interneuron ecto ns [spinal cord]
EE neuron, spinal motor ecto ns [spinal cord]
EE neuron, stratum oriens, lacunosum- ecto ns non-pyramidal, GABAergic (interneuron),
molaculare (O-LM) dendrites in stratum oriens, axons in stratum
lacunosum-molaculare [cerebral cortex]
EE neuron, striatal leptodendritic ecto ns [neostratum]
EE neuron, striatal microneuron ecto ns [neostratum]
EE neuron, striatal spidery ecto ns [neostratum]
EE neuron, striatal spiny ecto ns [neostratum]
EE neuron, thalamic relay ecto ns [thalamus]
EE neuron, thalamic reticular ecto ns interneuron [thalamus]
EE neuron, type I stellate cell ecto ns [cerebral cortex, cerebellar cortex, medulla
oblongata]
EE neuron, type II stellate cell ecto ns [cerebral cortex, cerebellar cortex, medulla
oblongata]
EE neuron, unipolar brush cell (UBC) ecto ns [cerebellar cortex, cochlear nucleus]
muscle tissuepskeletalpmyocyte
FF muscle cell, satellite, skeletal meso mm
FF muscle cell, skeletal, intermediate meso mm
FF muscle cell, skeletal, red cell (slow) meso mm
FF muscle cell, skeletal, white cell (fast) meso mm
muscle tissuepskeletalpspindle
GG muscle spindle, nuclear bag meso mm
GG muscle spindle, nuclear chain meso mm
muscle tissuepnon-skeletal
HH interstitial cell of Cajal, myenteric region meso ?mm pacemakers of the gastrointestinal musculature
(IC-MY) [intermuscular space between the circular and
longitudinal muscle layers of the stomach, small
intestine and large intestine ; Sanders et al., 1999] ;
considered by some to represent ECM secreting
support cells (category U) or PNS neurons
(category CC)
HH interstitial cell of Cajal, submucosal meso ?mm pacemakers of the gastrointestinal musculature
region (IC-SM) [submucosal surface of the circular muscles
of the large intestine ; Sanders et al., 1999] ;
considered by some to represent ECM secreting
support cells (category U) or PNS neurons
(category CC)
HH interstitial cell of Cajal, deep muscularis meso ?mm pacemakers of the gastrointestinal musculature
plexus region (IC-DMP) [small intestine ; Sanders et al., 1999] ; considered
by some to represent ECM secreting support cells
(category U) or PNS neurons (category CC)
454 Matthew K. Vickaryous and Brian K. Hall

Appendix 1 (cont.)

Assem- Germ Traditional

blage Cell type layer tissue type Notes

HH interstitial cell of Cajal, intramuscular meso ?mm pacemakers of the gastrointestinal musculature
region (IC-IM) [osesophagus, stomach and large intestine, as well
as the lower oesophageal, internal anal and ileo-
colonic sphincters ; Sanders et al., 1999] ; considered
by some to represent ECM secreting support cells
(category U) or PNS neurons (category CC)
HH muscle cell, cardiac fibre meso mm
HH muscle cell, cardiac ordinary meso mm
HH muscle cell, cardiac, nodal heart meso mm
HH muscle cell, smooth meso, ncrt mm may represent an undocumented diversity of cells
types (Freitas, 1999)
HH myoepithelial cell ecto ?ep contractile cells resembling smooth muscle cells
and found adjacent to exocrine glands and the
basement membrane
HH myofibroblast meso ? ?mm demonstrates features of both fibroblasts and
smooth muscle cells
HH Purkinje fibre cell meso mm

Appendix 2. List of characters used in the cladistic analysis

1. Endocrine cell : no (0) ; yes (1)

2. Desmosomes : absent (0) ; present (1)
3. Metabolism of biogenic amines : no (0) ; yes (1)
4. Large nucleus : no (0) ; yes (1)
5. Large number of granules : no (0) ; yes (1)
6. Extensive rough endoplasmic reticulum : no (0) ; yes (1)
7. Centrally located nucleus : no (0) ; yes (1)
8. Extensive Golgi apparatus : no (0) ; yes (1)
9. Abundance of free ribosomes : yes (0) ; no (1)
10. Abundance of mitochondria : no (0) ; yes (1)
11. Elongate cell morphology : no (0) ; yes (1)
12. Secretes extracellular matrix product : no (0) ; yes (1)
13. Peripherin : present (0) ; absent (1)
14. Migration route relative to the neural tube : dorsolateral (0) ; ventral (1)
15. Neural crest cells derived from trunk region : yes (0) ; no (1)
16. Labels with sympathoadrenal (SA) monoclonal antibodies 1–5 : no (0) ; yes (1)
17. Labels with osteonectin : no (0) ; yes (1)
18. Expresses chromogranin A (CgA) : no (0) ; yes (1)
19. Expresses neuron-specific enolase (NSE) : no (0) ; yes (1)
Human cell types 455

Appendix 3. Character-state distribution among eight neural-crest-derived cell types and one outgroup (undifferentiated
neural crest cell). Characters listed numerically to correspond to those in Appendix 2. Primitive states scored ‘ 0’, missing data ‘ ? ’,
and derived states ‘1’

characters

cell type 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

undifferentiated neural 0 0 ? ? 0 0 0 0 0 0 0 0 0 ? 0 0 0 0 0
crest cell
chromaffin cell 1 1 1 1 1 0 1 1 1 0 0 0 1 0 0 1 0 1 1
melanocyte 0 0 0 1 1 1 0 1 1 1 0 0 0 1 0 0 0 0 0
parafollicular cell 1 1 1 0 1 0 1 1 0 0 0 0 0 0 0 ? 0 1 1
Schwann cell 0 1 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0
osteocyte 0 0 0 1 0 1 1 1 0 ? 0 1 0 1 1 0 1 0 0
chondrocyte 0 0 0 1 0 1 1 1 0 ? 0 1 0 1 1 0 1 0 0
sympathetic neuron 1 1 1 1 ? 0 0 1 0 1 1 0 0 0 0 1 0 0 1
sensory neuron 1 1 0 1 ? 0 0 1 0 1 1 0 0 1 0 0 0 0 1

summary cladogram measures :

tree length=29 steps.
consistency index=0.6552.
retention index=0.6970.
re-scaled consistency index=0.4566.