Chapter 

20

Cell Communities: 
Tissues, Stem Cells, and 
Cancer

Essential Cell Biology, Fifth Edition  Copyright © 2019 W. W. Norton & Company
 CHAPTER CONTENTS

EXTRACELLULAR MATRIX AND CONNECTIVE TISSUES
EPITHELIAL SHEETS AND CELL JUNCTIONS
CH 19. Cell Junctions and the Extracellular Matrix 

STEM CELLS AND TISSUE RENEWAL
CH 22. Stem Cells and Tissue Renewal

CANCER
CH 20. Cancer
 STEM CELLS AND TISSUE RENEWAL

• Tissues Are Organized Mixtures of Many Cell Types

• Different Tissues Are Renewed at Different Rates
• Stem Cells and Proliferating Precursor Cells Generate a Continuous
Supply of Terminally Differentiated Cells
1. Stem cells and renewal in epithelial tissues
2. Fibroblasts and their transformations: the connective tissue
cell family
3. Genesis and regeneration of skeletal muscle
4. Blood vessels , lymphatics, and endothelial cells
5. A hierarchical stem-cell system: blood cell formation
• Specific Signals Maintain Stem-Cell Populations
• Stem Cells Can Be Used to Repair Lost or Damaged Tissues
• Induced Pluripotent Stem Cells Provide a Convenient Source of Human ES-
like Cells
• Mouse and Human Pluripotent Stem Cells Can Form Organoids in Culture
FIBROBLASTS AND THEIR TRANSFORMATIONS: THE CONNECTIVE‐TISSUE CELL 
FAMILY

The family of connective tissue cells. 
Fibroblasts Change Their Character in Response to Chemical and Physical Signals

Bone marrow stromal cells (fibroblasts)
 “mesenchymal stem cells” 

Control of fibroblast differentiation by the physical 
properties of the extracellular matrix
Osteoblasts Make Bone Matrix

The growth of cartilage
Osteoblasts Make Bone Matrix

Deposition of bone matrix by osteoblasts. 
Osteoblasts Make Bone Matrix

Trabecular and compact bone

Trabecular of an adult man 
(SEM image)
Bone Is Continually Remodeled by the Cells Within It

Osteoclasts
Bone Is Continually Remodeled by the Cells Within It

The remodeling of compact bone. 
Osteoclasts Are Controlled by Signals From Osteoblasts

Balance between osteoblast and osteoclast is crucial to 
maintain bone homeostasis

‐ Osteoporosis : excessive loss of bone matrix, weakening of bone
‐ Osteopetrosis : bone becomes excessively thick and dense
 STEM CELLS AND TISSUE RENEWAL

• Tissues Are Organized Mixtures of Many Cell Types

• Different Tissues Are Renewed at Different Rates
• Stem Cells and Proliferating Precursor Cells Generate a Continuous
Supply of Terminally Differentiated Cells
1. Stem cells and renewal in epithelial tissues
2. Fibroblasts and their transformations: the connective tissue cell
family
3. Genesis and regeneration of skeletal muscle
4. Blood vessels , lymphatics, and endothelial cells
5. A hierarchical stem-cell system: blood cell formation
• Specific Signals Maintain Stem-Cell Populations
• Stem Cells Can Be Used to Repair Lost or Damaged Tissues
• Induced Pluripotent Stem Cells Provide a Convenient Source of Human ES-
like Cells
• Mouse and Human Pluripotent Stem Cells Can Form Organoids in Culture
GENESIS AND REGENERATION OF SKELETAL MUSCLE

The four classes of muscle cells of a mammal
Myoblasts Fuse to Form New Skeletal Muscle Fibers

Myoblast fusion in culture. 

Skeletal muscle myosin (green), marking differentiated muscle cells
Some Myoblasts Persist as Quiescent Stem Cells in the Adult

Satellite cells repair 
skeletal muscle fibers 
Summary 1

• The family of connective tissue cells includes fibroblasts, cartilage cells, bone cells, fat 
cells, and smooth muscle cells. 
• Mesenchymal stem cells of bone marrow, transform into any of the other cells of the 
family 
• Cartilage and bone both consist of cells and solid matrix, that the cells secrete around 
themselves; chondrocytes in cartilage, osteoblasts in bone 
• Osteoblast secrete bone matrix, and signals that recruit monocytes from the circulation 
to become osteoclasts. 
• Bone undergoes remodeling through the activities of antagonistic classes of bone cells; 
osteoblast and osteoclasts
• Adult bone retains an ability to repair itself if fractured   

• Skeletal muscle fibers are one of the specialized cells for contraction, responsible for all 
voluntary movement
• Myoblasts proliferate extensively, but once they have fused, they can no longer divide
• Fusion follows myoblast differentiation into muscle fibers. 
• Some myoblasts persist in a quiescent state as satellite cells in adult muscle; stem cells of 
skeletal muscle 
 STEM CELLS AND TISSUE RENEWAL

• Tissues Are Organized Mixtures of Many Cell Types

• Different Tissues Are Renewed at Different Rates
• Stem Cells and Proliferating Precursor Cells Generate a Continuous
Supply of Terminally Differentiated Cells
1. Stem cells and renewal in epithelial tissues
2. Fibroblasts and their transformations: the connective tissue cell
family
3. Genesis and regeneration of skeletal muscle
4. Blood vessels , lymphatics, and endothelial cells
5. A hierarchical stem-cell system: blood cell formation
• Specific Signals Maintain Stem-Cell Populations
• Stem Cells Can Be Used to Repair Lost or Damaged Tissues
• Induced Pluripotent Stem Cells Provide a Convenient Source of Human ES-
like Cells
• Mouse and Human Pluripotent Stem Cells Can Form Organoids in Culture
BLOOD VESSELS, LYMPHATICS, AND ENDOTHELIAL CELLS

Endothelial Cells Line All 
Blood Vessels and Lymphatics

Diagram of small artery
Endothelial Cells Line All Blood Vessels and Lymphatics

Capillaries
Endothelial Cells Line All Blood Vessels and Lymphatics

Pericytes

Arteries, veins, capillaries, and 
lymphatics all developed from small 
vessels constructed of endothelial 
cells and a basal lamina: 

Connective tissue and smooth 
muscle are added later, under the 
influence of signals from the 
endothelial cells. 
Endothelial Tip Cells Pioneer Angiogenesis

Angiogenesis Angiogenesis in mouse 
embryonic retina

*Endothelial tip cells, pioneer of the growth of normal capillaries, and respond 
to signals in the environment (ex. VEGF‐ vascular endothelial growth factor) 
Tissues Requiring a Blood Supply Release VEGF

New capillary formation in respond to wounding. 
Tissues Requiring a Blood Supply Release VEGF

Regulatory mechanism 
controlling blood vessel 
growth according to a 
tissue’s need for oxygen

Signals from Endothelial Cells Control Recruitment of Pericytes and Smooth Muscle 
Cells to Form the Vessel Wall
PDGF‐B (platelet‐derived growth factor‐B) secreted by endothelial cells, recruits pericytes
and smooth muscle cells
(Video: Angiogenesis)
 STEM CELLS AND TISSUE RENEWAL

• Tissues Are Organized Mixtures of Many Cell Types

• Different Tissues Are Renewed at Different Rates
• Stem Cells and Proliferating Precursor Cells Generate a Continuous
Supply of Terminally Differentiated Cells
1. Stem cells and renewal in epithelial tissues
2. Fibroblasts and their transformations: the connective tissue cell
family
3. Genesis and regeneration of skeletal muscle
4. Blood vessels , lymphatics, and endothelial cells
5. A hierarchical stem‐cell system: blood cell formation
• Specific Signals Maintain Stem-Cell Populations
• Stem Cells Can Be Used to Repair Lost or Damaged Tissues
• Induced Pluripotent Stem Cells Provide a Convenient Source of Human ES-
like Cells
• Mouse and Human Pluripotent Stem Cells Can Form Organoids in Culture
A single type of stem cell gives rise to several types of differentiated progeny

Stem cell of the intestine
‐> absorptive, goblet, several other secretory cell types

The blood‐cell formation (hemopoiesis) in bone marrow 
hematopoietic stem cell ‐> all kinds of blood cells
Blood contains many circulating cell types, all derived from a
single type of stem cell.
A HIERARCHICAL STEM‐CELL SYSTEM: BLOOD CELL FORMATION

Red Blood Cells Are 
All Alike; White 
Blood Cells Can Be 
Grouped in Three 
Main Classes
Red Blood Cells Are All Alike; White Blood Cells Can Be Grouped in Three Main 
Classes
A hemopoietic stem cell divides to generate more stem cells as well as
precursor cells (not shown) that proliferate and differentiate into the
mature blood cell types found in the circulation.
The Production of Each Type of Blood Cell in the Bone Marrow Is Individually 
Controlled

Chemotaxis of white blood 
cells to damaged tissue 
Bone Marrow Contains Multipotent Hematopoietic Stem Cells, Able to Give Rise to 
All Classes of Blood Cells

A megakaryocyte among other developing blood cells in the bone marrow
Bone Marrow Contains Multipotent Hematopoietic Stem Cells, Able to Give Rise to 
All Classes of Blood Cells
Stem Cells Depend on Contact Signals From Stromal Cells

Dependence of hematopoietic stem cells 
on contact with stromal cells

• Contact dependent interaction between the 
Kit receptor and its ligand is one of several 
signaling mechanisms involved in 
hematopoietic stem cell maintenance. 
*SCF (stem‐cell factor)

• The factors supporting hematopoiesis, 
are glycoproteins usually called colony‐
forming factors (CSFs)
Erythropoiesis Depends on the Hormone Erythropoietin

A developing red blood cell (erythroblast)

• Erythropoietin, a glycoprotein, acts as hormone 

‐ Regulate erythropoiesis, the formation of 
erythrocytes (red blood cells)

‐ Immature erythrocytes (reticulocytes)
The Behavior of a Hematopoietic Cell Depends Partly on Chance

Some of parameters through 
which the production of blood 
cells of a specific type might be 
regulated 

• CSFs promote the 
production of colonies of 
differentiated blood cells

• Hematopoietic cells are 
die by apoptosis in the 
absence of CSFs
: regulation of cell survival 
is as important as 
regulation of cell 
proliferation
Summary 2

• Endothelial cells are the fundamental elements of the vascular system. 
• New vessels originate as endothelial sprouts from the walls of existing small vessel 
• Hypoxia induces angiogenesis, by regulation of VEGF signaling pathways. 

• The many types of blood cells are derived from a common multipotent stem cell
• Hematopoietic stem cells are found in bone marrow, and they depend on the 
marrow stromal (connective‐tissue) derived signals to maintain their stemness. 
• The stem cells normally divide infrequently to produce more stem cells, and various 
committed progenitor cells (transit amplifying cells), which give one or a few types 
of blood cells. 
• The committed progenitor cells divide extensively under the control of various 
signaling factors (ex. CSFs) and then terminally differentiate into mature blood cells, 
which die after several days or week.
• Apoptotic cell death is controlled by CSFs, play a central role in regulating the 
number of mature differentiated blood cells.