“You’re not supposed to be able to do stuff

while you sleep,” says Delphine Oudiette, a

cognitive scientist at the Paris Brain Institute
and a co-author of the study. Historically, the
definition of sleep is that consciousness of
your environment halts, she adds. “It means
you don’t react to the external world.”

Dream time
A few years ago, however, Oudiette began
questioning this definition after she and her
team conducted an experiment in which they
were able to communicate with people who are
aware that they are dreaming while they sleep
— otherwise known as lucid dreamers. During
DENNIS KUNKEL MICROSCOPY/SPL

these people’s dreams, experimenters were

able to ask questions and get responses through
eye and facial-muscle movements (K. R. Kon-
koly. et al. Curr. Biol. 31, 1417–1427; 2021).
Karen Konkoly, a co-author of that study and
a cognitive scientist at Northwestern Univer-
sity in Evanston, Illinois, says that after the
paper came out, “it was a big open question Insights into brain cells could improve understanding of diseases and cognition.
in our minds whether communication would

LARGEST MAP OF HUMAN

be possible with non-lucid dreamers”.
So Oudiette continued with the work. In her

BRAIN YET REVEALS CELLS

latest study, she and her colleagues observed
27 people with narcolepsy — characterized by

UNKNOWN TO SCIENCE
daytime sleepiness and a high frequency of
lucid dreams — and 22 people without the con-
dition. While they were sleeping, participants
were repeatedly asked to frown or smile. All of
them responded accurately to at least 70% of Researchers catalogue more than 3,000 types
these prompts.
Overall response rates were higher for all of cell in most complex known organ.
participants during REM (rapid eye move-
By Gemma Conroy

ment) sleep, when the deepest sleep occurs
but the brain remains quite active, than during
other sleep stages. The researchers tracked
participants’ brain activity during the exper-
iments using electroencephalography (EEG),
which captures signals from electrodes placed
along a person’s scalp.
A research evolution
What this shows is that “you have some phys-
iological states that are more favourable to
opening the [window shade] to the external
world”, Oudiette says.
Using similar experiments, researchers
might gain a better understanding of var-
ious sleep disorders, including insomnia
and sleep walking, she says. And they might
begin to identify the parts of the brain that are
active during sleep, and how those relate to
consciousness.
This study is part of a larger evolution in the
field of sleep research, says Mélanie Strauss, a
neurologist and cognitive scientist at Erasmus
Hospital in Brussels. Researchers are moving
away from monitoring sleep mainly with EEG
and towards “fine grained” approaches that
combine EEG with various tasks and stimuli
— a strategy that could help to shed light on
specific diseases or conditions, she says.
R
esearchers have created the larg-
est atlas of human brain cells so far,
revealing more than 3,000 cell types
— many of which are new to science.
The work, published in a package of
21 papers in Science, Science Advances and Sci-
ence Translational Medicine (see go.nature.
com/3qoiish), will aid the study of diseases,
cognition and what makes us human, among
other things, say the authors.
The enormous cell atlas offers a detailed
snapshot of the most complex known organ.
“It’s highly significant,” says Anthony Hannan, a
neuroscientist at the Florey Institute of Neuro­
science and Mental Health in Melbourne, Aus-
tralia. Researchers have previously mapped
the human brain with techniques such as
magnetic resonance imaging, but this is the
first atlas of the whole human brain at the sin-
gle-cell level, showing its intricate molecular
interactions, he adds. “These types of atlases
really are laying the groundwork for a much
better understanding of the human brain.”
The research is part of the US National
Institutes of Health’s Brain Research through
Advancing Innovative Neurotechnologies
Initiative — Cell Census Network (BICCN), a
collaboration between hundreds of scientists.
The programme’s goals include cataloguing
brain cell types across humans, non-human
primates and mice to understand the cellular
mechanisms behind poorly understood brain
disorders. The data from the 21 studies have
been made publicly available on the Neuro-
science Multi-omic Archive online repository.
Cellular menagerie
Kimberly Siletti, a neuroscientist now at the
University Medical Center Utrecht in the Neth-
erlands, and her team laid the cornerstone
for the atlas by sequencing the RNA of more
than 3 million individual cells from 106 loca-
tions across the brain, using tissue from three
deceased male donors1. They also included
one motor cortex dissection from a female
donor that had been used in previous stud-
ies. Their analysis documented 461 broad cat­
egories of brain cell that included more than
3,000 subtypes. “I was surprised at how many
different cell types there were,” says Siletti.
Neurons — cells in the brain and nervous
system that send and receive signals — varied
widely in different parts of the brain, suggest-
ing different functions and developmental
histories. The mix of neurons and other cell
types also differed across each region; some

Nature | Vol 622 | 26 October 2023 | 679

News in focus
cells were found only in specific locations.
The brainstem — a relatively under-studied
structure connecting the brain to the spinal
cord — harboured a particularly high number
of neuron types, says study co-author Sten
Linnarsson, a molecular systems biologist at
the Karolinska Institute in Stockholm. “One
of the big surprises here is how incredibly
complex the brainstem is.”
Other studies drilled into the mechanisms
of gene regulation and expression in different
cells. Joseph Ecker, a molecular biologist at the
Salk Institute for Biological Studies in La Jolla,
California, and his colleagues investigated the
brain through an epigenetic lens using tissue
samples from the same three donors2. They
analysed chemical markers that switch genes
on or off in more than 500,000 cells. The vari-
ous molecules that acted as switches enabled
the team to identify nearly 200 brain cell types.
Even the same gene in the same type of cell
could have different characteristics across the
brain. One gene was turned on with one switch
at the front of the brain and with another at
the back. “There are remarkable regional dif-
ferences,” says study co-author Wei Tian, a
computational biologist at the Salk Institute.
Pinpointing the switches that activate or
block gene expression in brain cells could Quantum dots emit various wavelengths of light on the basis of their size.
be useful for diagnosing brain disorders and

MEET THE UNSUNG

developing tailored treatments, says Ecker.
“That’s another tool that comes out of the

SCIENTISTS BEHIND THE

toolbox we’re building,” he says.

Disease risk
How genetic switches might contribute to dis-
ease risk was also a focus for Bing Ren, a molec-
ular biologist at the University of California,
QUANTUM-DOT NOBEL
San Diego, and his team3. The researchers These researchers worked with this year’s chemistry
uncovered links between certain cell types and
neuropsychiatric disorders, including bipolar laureates to develop the prized nanocrystals.
disorder, depression and schizophrenia.
By Neil Savage

Ren and his colleagues used the cell-type
data to predict how the genetic switches
influence gene regulation and increase the
risk of neurological diseases. For instance,
in cells called microglia, which clear away
dead or damaged cells, the presence of some
genetic switches was strongly linked to risks
of Alzheimer’s disease. Such findings can be
used to test whether particular genes or faulty
switches contribute directly to the onset of dis-
ease. “This is made possible because we have
N
obel prizewinners almost never work
in isolation. They might be the driv-
ing force behind their award-winning
discoveries, but a whole host of col-
laborators, postdoctoral fellows
and graduate students helped to realize their
vision in the laboratory.
Where do those scientists end up? What is
it like for them to be part of a celebrated piece
together in our graduate studies at the time
that [Moungi] began his life as a professor,”
Murray says. Bawendi had himself just finished
a stint as a postdoc, working with Brus at the
innovative Bell Laboratories in Murray Hill,
New Jersey.
Murray loved the process of building a
research lab from scratch. He and another
graduate student — David Norris, who is now
a materials engineer at the Swiss Federal Insti-
tute of Technology in Zurich — helped Bawendi
NATL ENERGY TECHNOLOGY LAB./US DEPT OF ENERGY/SPL

— for the first time — delineated the genetic
switches for hundreds of different cell types,”
says Ren.
The next step for the BICCN team is to
sequence more cells from all parts of the brain,
says Ren. The researchers will also work with
more tissue samples to build a picture of how
the human brain can vary across populations
and ages. “This is only the beginning,” he says.
1. Siletti, K. et al. Science 382, eadd7046 (2023).
2. Tian, W. et al. Science 382, eadf5357 (2023).
3. Li, Y. E. et al. Science 382, eadf7044 (2023).
of scientific history? Nature caught up with
some of the researchers who contributed to
the work recognized by this year’s Nobel Prize
in Chemistry, given to quantum-dot pioneers
Moungi Bawendi at the Massachusetts Insti-
tute of Technology (MIT) in Cambridge, Louis
Brus at Columbia University in New York City
and Alexei Ekimov, previously at New York-
based company Nanocrystals Technology.
Christopher Murray was among the first
batch of graduate students that Bawendi hired
for his lab at MIT in 1990. “We began our lives
to work out the process of synthesizing quan-
tum dots. Before this, researchers including
Ekimov and Brus had observed the dots —
nanoscale semiconductor crystals — emitting
various wavelengths of light, and worked out
that the wavelengths depended on the dots’
size. But they hadn’t yet developed the chemis-
try to produce them in a controlled way.
Bawendi’s group developed a strategy that
encouraged semiconductor nanoparticles to
assemble themselves into consistent, com-
plex structures. The work would eventually be

680 | Nature | Vol 622 | 26 October 2023