ABSTRACT
The
vertebrate
spinal
cord
comprises
multiple
functionally
distinct
neuronal
cell
types
arranged
in
characteristic
positions.
During
development,
these
different
of
neurons
differentiate
from
transcriptionally
neural
progenitors
that
are
arrayed
discrete
domains
along
the
dorsal-ventral
and
anterior-posterior
axes
embryonic
cord.
This
organization
arises
response
to
morphogen
gradients
acting
upstream
a
gene
regulatory
network,
architecture
which
determines
spatial
temporal
pattern
expression.
In
recent
years,
substantial
progress
has
been
made
deciphering
network
underlies
specification
progenitor
identities.
this
Review,
we
outline
how
identities
established
patterning
systems,
novel
experimental
approaches
study
emergence
function
diversity
Nature,
Год журнала:
2023,
Номер
614(7949), С. 742 - 751
Опубликована: Фев. 8, 2023
Abstract
Cell
identity
is
governed
by
the
complex
regulation
of
gene
expression,
represented
as
gene-regulatory
networks
1
.
Here
we
use
inferred
from
single-cell
multi-omics
data
to
perform
in
silico
transcription
factor
perturbations,
simulating
consequent
changes
cell
using
only
unperturbed
wild-type
data.
We
apply
this
machine-learning-based
approach,
CellOracle,
well-established
paradigms—mouse
and
human
haematopoiesis,
zebrafish
embryogenesis—and
correctly
model
reported
phenotype
that
occur
a
result
perturbation.
Through
systematic
perturbation
developing
zebrafish,
simulate
experimentally
validate
previously
unreported
results
loss
noto
,
an
established
notochord
regulator.
Furthermore,
identify
axial
mesoderm
regulator,
lhx1a
Together,
these
show
CellOracle
can
be
used
analyse
factors,
provide
mechanistic
insights
into
development
differentiation.
ABSTRACT
The
vertebrate
spinal
cord
comprises
multiple
functionally
distinct
neuronal
cell
types
arranged
in
characteristic
positions.
During
development,
these
different
of
neurons
differentiate
from
transcriptionally
neural
progenitors
that
are
arrayed
discrete
domains
along
the
dorsal-ventral
and
anterior-posterior
axes
embryonic
cord.
This
organization
arises
response
to
morphogen
gradients
acting
upstream
a
gene
regulatory
network,
architecture
which
determines
spatial
temporal
pattern
expression.
In
recent
years,
substantial
progress
has
been
made
deciphering
network
underlies
specification
progenitor
identities.
this
Review,
we
outline
how
identities
established
patterning
systems,
novel
experimental
approaches
study
emergence
function
diversity
