ABSTRACT
Dorsal
interneurons
(dIs)
in
the
spinal
cord
encode
perception
of
touch,
pain,
heat,
itchiness
and
proprioception.
Previous
studies
using
genetic
strategies
animal
models
have
revealed
important
insights
into
dI
development,
but
molecular
details
how
dIs
arise
as
distinct
populations
neurons
remain
incomplete.
We
developed
a
resource
to
investigate
fate
specification
by
combining
single-cell
RNA-Seq
atlas
mouse
embryonic
stem
cell-derived
with
pseudotime
analyses.
To
validate
this
silico
useful
tool,
we
used
it
first
identify
genes
that
are
candidates
for
directing
transition
states
lead
lineage
trajectories,
then
validated
them
situ
hybridization
analyses
developing
vivo.
also
identified
an
endpoint
dI5
trajectory
found
become
more
transcriptionally
homogeneous
during
terminal
differentiation.
This
study
introduces
valuable
tool
further
discovery
about
timing
gene
expression
differentiation
demonstrates
its
utility
clarifying
relationships.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Апрель 28, 2022
Abstract
During
embryonic
development,
epithelial
cell
blocks
called
somites
are
periodically
formed
according
to
the
segmentation
clock,
becoming
foundation
for
segmental
pattern
of
vertebral
column.
The
process
somitogenesis
has
recently
been
recapitulated
with
murine
and
human
pluripotent
stem
cells.
However,
an
in
vitro
model
coupled
clock
epithelialization
is
still
missing.
Here,
we
report
generation
somitoids,
organoids
that
form
pairs
somite-like
structures.
Somitoids
display
clear
oscillations
coincide
presomitic
mesoderm.
resulting
show
anterior-posterior
apical-basal
polarities.
Matrigel
essential
but
dispensable
differentiation
into
somite
size
rather
constant,
irrespective
initial
number.
amount
WNT
signaling
instructs
proportion
mesodermal
lineages
somitoids.
provide
a
novel
platform
study
somitogenesis.
Cell stem cell,
Год журнала:
2023,
Номер
30(7), С. 938 - 949.e7
Опубликована: Июнь 20, 2023
Differential
speeds
in
biochemical
reactions
have
been
proposed
to
be
responsible
for
the
differences
developmental
tempo
between
mice
and
humans.
However,
underlying
mechanism
controlling
species-specific
kinetics
remains
determined.
Using
vitro
differentiation
of
pluripotent
stem
cells,
we
recapitulated
segmentation
clocks
diverse
mammalian
species
varying
body
weight
taxa:
marmoset,
rabbit,
cattle,
rhinoceros.
Together
with
mouse
human,
clock
periods
six
did
not
scale
animal
weight,
but
embryogenesis
length.
The
core
gene
HES7
displayed
clear
scaling
period.
cellular
metabolic
rates
show
an
evident
correlation.
Instead,
genes
involving
showed
expression
pattern
that
scales
Altogether,
our
cell
zoo
uncovered
general
laws
governing
tempo.
Considerable
phenotypic
variation
under
identical
culture
conditions
limits
the
potential
of
stem-cell-based
embryo
models
(SEMs)
in
basic
and
applied
research.
The
biological
processes
causing
this
seemingly
stochastic
remain
unclear.
Here,
we
investigated
roots
by
parallel
recording
transcriptomic
states
morphological
history
individual
structures
modeling
embryonic
trunk
formation.
Machine
learning
integration
time-resolved
single-cell
RNA
sequencing
with
imaging-based
profiling
identified
early
features
predictive
end
states.
Leveraging
power
revealed
that
imbalance
oxidative
phosphorylation
glycolysis
results
aberrant
morphology
a
neural
lineage
bias,
which
confirmed
metabolic
measurements.
Accordingly,
interventions
improved
Collectively,
our
work
establishes
divergent
as
drivers
offers
broadly
applicable
framework
to
chart
predict
organoids
SEMs.
strategy
can
be
used
identify
control
underlying
processes,
ultimately
increasing
reproducibility.
Nature Genetics,
Год журнала:
2023,
Номер
55(7), С. 1164 - 1175
Опубликована: Июнь 15, 2023
During
development,
Hox
genes
are
temporally
activated
according
to
their
relative
positions
on
clusters,
contributing
the
proper
identities
of
structures
along
rostrocaudal
axis.
To
understand
mechanism
underlying
this
timer,
we
used
mouse
embryonic
stem
cell-derived
stembryos.
Following
Wnt
signaling,
process
involves
transcriptional
initiation
at
anterior
part
cluster
and
a
concomitant
loading
cohesin
complexes
enriched
transcribed
DNA
segments,
that
is,
with
an
asymmetric
distribution
favoring
cluster.
Chromatin
extrusion
then
occurs
successively
more
posterior
CTCF
sites
acting
as
transient
insulators,
thus
generating
progressive
time
delay
in
activation
posterior-located
due
long-range
contacts
flanking
topologically
associating
domain.
Mutant
stembryos
support
model
reveal
presence
evolutionary
conserved
regularly
spaced
intergenic
controls
precision
pace
temporal
mechanism.
Developmental Cell,
Год журнала:
2024,
Номер
59(12), С. 1489 - 1505.e14
Опубликована: Апрель 4, 2024
Embryogenesis
requires
substantial
coordination
to
translate
genetic
programs
the
collective
behavior
of
differentiating
cells,
but
understanding
how
cellular
decisions
control
tissue
morphology
remains
conceptually
and
technically
challenging.
Here,
we
combine
continuous
Cas9-based
molecular
recording
with
a
mouse
embryonic
stem
cell-based
model
trunk
build
single-cell
phylogenies
that
describe
transient,
multipotent
neuro-mesodermal
progenitors
(NMPs)
as
they
commit
into
neural
somitic
cell
types.
We
find
NMPs
show
subtle
transcriptional
signatures
related
their
recent
differentiation
contribute
downstream
lineages
through
surprisingly
broad
distribution
individual
fate
outcomes.
Although
decision-making
can
be
heavily
influenced
by
environmental
cues
induce
morphological
phenotypes,
axial
intrinsically
mature
over
developmental
time
favor
lineage.
Using
these
data,
present
an
experimental
analytical
framework
for
exploring
non-homeostatic
dynamics
transient
progenitor
populations
shape
complex
tissues
during
critical
windows.
Developmental Biology,
Год журнала:
2022,
Номер
484, С. 75 - 87
Опубликована: Фев. 17, 2022
Ever
since
their
first
report
in
1984,
Antennapedia-type
homeobox
(Hox)
genes
have
been
involved
such
a
series
of
interesting
observations,
particular
due
to
conserved
clustered
organization
between
vertebrates
and
arthropods,
that
one
may
legitimately
wonder
about
the
origin
this
heuristic
value.
In
essay,
I
consider
different
examples
where
Hox
gene
clusters
instrumental
providing
conceptual
advances,
taken
from
various
fields
research
mostly
involving
vertebrate
embryos.
These
touch
upon
our
understanding
genomic
evolution,
revisiting
19th
century
views
on
relationships
development
evolution
building
new
framework
understand
long-range
pleiotropic
regulation
during
development.
then
discuss
whether
high
value
family,
when
considered
as
an
epistemic
object,
is
related
its
structure
(and
absence
thereof
some
animal
species)
and,
if
so,
what
it
genetic
oddities
made
them
so
generous
scientific
community
with
information.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 4, 2025
Abstract
Embryogenesis
integrates
morphogenesis—coordinated
cell
movements—with
morphogen
patterning
and
differentiation.
While
largely
studied
independently,
morphogenesis
often
unfold
simultaneously
in
early
embryos.
Yet,
how
movements
affect
remains
unclear,
as
most
pattern
formation
models
assume
static
tissues.
We
address
this
gap
by
developing
a
mathematical
framework
for
dynamic
tissues,
reformulating
advection-reaction-diffusion
cells’
reference
frames—the
natural
signal
interpretation
fate
decisions.
This
(i)
elucidates
mediates
transport
compartmentalization:
multicellular
attractors
enhance
cell-cell
diffusive
transport,
while
repellers
act
barriers,
affecting
induction
bifurcations.
(ii)
It
formalizes
signaling
ranges
deconfounding
morphogenetic
identifying
which
cells
can
communicate.
(iii)
provides
two
nondimensional
numbers—typically
distinct
from
the
Péclet
number—to
assess
when
where
is
relevant
patterning.
(iv)
generative
role
of
density
dynamics
apply
to
classic
models,
motifs,
avian
gastrulation
data.
Broadly,
our
work
quantitative
perspective
rationalize
tissue
synthetic
