SCIENTIST TO WATCHAssistant Professor, Head of Laboratory of Single-Cell Genomics
and Population Dynamics, The Rockefeller UniversityBY LISA WINTERJunyue Cao: Cell Mapper
MATTHEW SEPTIMUS, THE ROCKEFELLER UNIVERSITYF
rom the time he was nine years old,
growing up in a small town outside of
Beijing, Junyue Cao knew he was going
to be a scientist. Raised by two middle school
teachers—his mother and father taught Chi-
nese and chemistry, respectively—he had
access to equipment and libraries and the
freedom to explore his curiosities, Cao says.
He read science books along with science
fiction, fueling a natural inquisitiveness that
saw him through a rigorous curriculum at a
prestigious high school and into a bachelor’s
degree in biology at nearby Peking Univer-
sity in 2010.
Throughout his education, Cao was driven
by one main question: Why do people die
when they get old? To understand the cellu-
lar mechanics of aging, he wanted to map all
of the potential fates a cell could have, start-
ing with a single fertilized egg. But humans
are complex—their bodies contain trillions
of cells, each of which can differentiate into
thousands of different cell types. Instead,
when Cao started his PhD studies in 2014
at Caltech, he began working on single-cell
genetics with a simpler organism, the nema-
tode C. elegans, which has 27 cell types and
only about 1,000 somatic cells in total when
fully grown.
The scale of these projects remained rel-
atively small, as existing technologies could
only profile three to five cells at a time, with a
price tag of around $100 per cell. A year later,
Cao transferred to the University of Wash-
ington (UW) in Seattle, joining geneticist Jay
Shendure’s lab. There, he added mouse and
human cells to his repertoire, eventually study-
ing hundreds of cell types. Cao developed
several novel protocols for high-throughput,
single-cell genomics techniques, focusing
specifically on gene expression, transcrip-
tomics approaches, and messenger RNA
expression, to track the fate of cells and
study cell proliferation in a developing organ-ism (Science, 357:661–67, 2017; Science,
361:1380–85, 2018; Nat Biotechnol, 38:980–
88, 2020). Today, for less than a cent per cell,
these new tools can profile more than 2 mil-
lion cells simultaneously, making it easier to
see where the effects of aging manifest and
accumulate, Cao says, and potentially prov-
ing useful for studying the onset of disease.
After arriving in Seattle, Cao “immedi-
ately made a huge splash,” says Sanjay Srivat-
san, a postdoc at UW who was then enrolled
in the university’s MD/PhD program. These
techniques made it possible for Cao to pro-
duce an atlas for each cell type found in mice,
from neurons to intestinal cells, that includes
a list of all of the possible outcomes for each
cell line. Specifically, Cao barcoded cells of
mouse embryos at five stages of develop-
ment and used a process called single-cell
combinatorial indexing to create digital mod-
els of each cell’s trajectory (Nature, 566:496–
502, 2019). Cao’s work “made it very clear
that people should be thinking on this scale,
and since then, people really have been,”
Srivatsan says.
After defending his dissertation and launch-
ing an interactive version of the mouse atlas
in 2019, Cao stayed in Shendure’s lab as a
postdoc until he accepted an assistant profes-
sorship at The Rockefeller University the fol-
lowing year. Launching his lab at a time when
in-person contact was limited due to the
COVID-19 pandemic made collaborations
hard to establish. Cao credits the univer-
sity with being supportive, and notes that
his lab now includes more than a dozen
people. “[They] are really brilliant, and
I’m grateful to have the chance to work
with them,” he says.
Alexander Tarakhovsky, an epi-
geneticist at Rockefeller, lauds Cao’s
“old-fashioned enthusiasm for sci-
ence” combined with his pen-
chant for developing cutting-edgetechnology “that is so essential for our com-
prehension of gene regulation and cell-cell
interaction,” he tells The Scientist. Cao’s work,
he adds, “is definitely playing a key role in
building up the resources” to help move those
fields forward.
Outside of his passion for research, Cao
also prioritizes time with his two young
children, ages seven and two years old. He
says that the family enjoys the energy of
bustling New York City, but also looks for-
ward to the low-key time they spend at their
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