Nature Cell Biology,
Год журнала:
2024,
Номер
26(6), С. 903 - 916
Опубликована: Май 3, 2024
Dynamic
changes
in
mechanical
microenvironments,
such
as
cell
crowding,
regulate
lineage
fates
well
proliferation.
Although
regulatory
mechanisms
for
contact
inhibition
of
proliferation
have
been
extensively
studied,
it
remains
unclear
how
crowding
induces
specification.
Here
we
found
that
a
well-known
oncogene,
ETS
variant
transcription
factor
4
(ETV4),
serves
molecular
transducer
links
microenvironments
and
gene
expression.
In
growing
epithelium
human
embryonic
stem
cells,
dynamics
is
translated
into
ETV4
expression,
serving
pre-pattern
future
fates.
A
switch-like
inactivation
by
derepresses
the
potential
neuroectoderm
differentiation
epithelia.
Mechanistically,
inactivates
integrin-actomyosin
pathway
blocks
endocytosis
fibroblast
growth
receptors
(FGFRs).
The
disrupted
FGFR
marked
decrease
protein
stability
through
ERK
inactivation.
Mathematical
modelling
demonstrates
density
precisely
determines
spatiotemporal
expression
pattern
and,
consequently,
timing
geometry
development.
Our
findings
suggest
drives
specification
using
key
transducer.
Life Science Alliance,
Год журнала:
2023,
Номер
6(8), С. e202201706 - e202201706
Опубликована: Май 22, 2023
Human
germline-soma
segregation
occurs
during
weeks
2-3
in
gastrulating
embryos.
Although
direct
studies
are
hindered,
here,
we
investigate
the
dynamics
of
human
primordial
germ
cell
(PGCs)
specification
using
vitro
models
with
temporally
resolved
single-cell
transcriptomics
and
in-depth
characterisation
vivo
datasets
from
nonhuman
primates,
including
a
3D
marmoset
reference
atlas.
We
elucidate
molecular
signature
for
transient
gain
competence
fate
peri-implantation
epiblast
development.
Furthermore,
show
that
both
PGCs
amnion
arise
transcriptionally
similar
TFAP2A-positive
progenitors
at
posterior
end
embryo.
Notably,
genetic
loss
function
experiments
shows
TFAP2A
is
crucial
initiating
PGC
without
detectably
affecting
subsequently
replaced
by
TFAP2C
as
an
essential
component
network
fate.
Accordingly,
amniotic
cells
continue
to
emerge
epiblast,
but
importantly,
this
also
source
nascent
PGCs.
In
the
nascent
mesoderm,
TBXT
expression
must
be
precisely
regulated
to
ensure
that
cells
exit
primitive
streak
and
pattern
anterior-posterior
axis,
but
how
varying
dosage
informs
morphogenesis
is
not
well
understood.
this
study,
we
define
transcriptional
consequences
of
reduction
during
early
human
gastrulation
using
induced
pluripotent
stem
cell
models
mesoderm
differentiation.
Multi-omic
single-nucleus
RNA
ATAC
sequencing
2D
gastruloids
comprising
wild-type,
heterozygous
or
null
reveal
does
compromise
ability
a
differentiate
into
instead
directly
influences
temporal
progression
epithelial-to-mesenchymal
transition
with
wild
type
transitioning
first,
followed
by
then
null.
By
differentiating
in
monolayer
format,
further
illustrate
impacts
persistence
junctional
proteins
cell-cell
adhesions.
These
results
demonstrate
can
decoupled
from
acquisition
mesodermal
identity
gastrula
shed
light
on
mechanisms
underlying
embryogenesis.
Stem Cell Reports,
Год журнала:
2021,
Номер
16(5), С. 1117 - 1141
Опубликована: Май 1, 2021
Detailed
studies
of
the
embryo
allow
an
increasingly
mechanistic
understanding
development,
which
has
proved
profound
relevance
to
human
disease.
The
last
decade
seen
in
vitro
cultured
stem
cell-based
models
development
flourish,
provide
alternative
for
accessible
experimentation.
However,
usefulness
any
model
will
be
determined
by
how
accurately
it
reflects
vivo
embryonic
and/or
extent
facilitates
new
discoveries.
Stringent
benchmarking
is
thus
important
consideration
this
growing
field.
Here
we
overview
means
evaluate
both
properties
cells,
building
blocks
most
models,
as
well
current
and
future
models.
ABSTRACT
During
embryogenesis,
organisms
acquire
their
shape
given
boundary
conditions
that
impose
geometrical,
mechanical
and
biochemical
constraints.
A
detailed
integrative
understanding
how
these
morphogenetic
information
modules
pattern
the
mammalian
embryo
is
still
lacking,
mostly
owing
to
inaccessibility
of
in
vivo
for
direct
observation
manipulation.
These
impediments
are
circumvented
by
developmental
engineering
embryo-like
structures
(stembryos)
from
pluripotent
stem
cells
easy
access,
track,
manipulate
scale.
Here,
we
explain
unlocking
distinct
levels
architecture
through
controlled
modulations
cellular
environment
enables
identification
minimal
sets
inputs
necessary
embryo.
We
detail
this
can
be
complemented
with
precise
measurements
manipulations
tissue
biochemistry,
mechanics
geometry
across
spatial
temporal
scales
provide
insights
into
mechanochemical
feedback
loops
governing
morphogenesis.
Finally,
discuss
how,
even
absence
active
manipulations,
stembryos
display
intrinsic
phenotypic
variability
leveraged
define
constraints
ensure
reproducible
morphogenesis
vivo.
Experimental & Molecular Medicine,
Год журнала:
2023,
Номер
55(10), С. 2127 - 2137
Опубликована: Окт. 2, 2023
Abstract
Recent
discoveries
in
stem
cell
and
developmental
biology
have
introduced
a
new
era
marked
by
the
generation
of
vitro
models
that
recapitulate
early
mammalian
development,
providing
unprecedented
opportunities
for
extensive
research
embryogenesis.
Here,
we
present
an
overview
current
techniques
model
embryogenesis,
specifically
noting
created
from
cells
derived
two
significant
species:
Homo
sapiens
,
its
high
relevance,
Mus
musculus
historically
common
technically
advanced
organism.
We
aim
to
provide
holistic
understanding
these
tracing
historical
background
progress
made
discussing
fundamental
underlying
principles.
At
each
stage,
corresponding
vivo
embryo
further
discuss
how
may
be
used
diseases.
Through
discussion
as
well
their
potential
applications
future
challenges,
hope
demonstrate
innovative
advances
developed
actualize
clinical
practice.
