Science Advances,
Journal Year:
2025,
Volume and Issue:
11(13)
Published: March 26, 2025
Most
advances
in
early
human
postimplantation
development
depend
on
animal
studies
and
stem
cell–based
embryo
models.
Here,
we
present
self-organized
three-dimensional
gastruloids
(hGs)
derived
from
embryonic
cells.
The
transcriptome
profile
of
day
3
hGs
aligned
with
Carnegie
stage
7
gastrula,
cell
types
differentiation
trajectories
consistent
gastrulation.
Notably,
observed
the
emergence
nascent
primordial
germ
cell–like
cells
(PGCLCs),
but
without
exogenous
bone
morphogenetic
protein
(BMP)
signaling,
which
is
essential
for
PGCLC
fate.
A
mutation
ISL1
gene
affects
amnion-like
leads
to
a
loss
PGCLCs;
addition
BMP2
rescues
fate,
indicating
that
amnion
may
provide
endogenous
BMP
signaling.
Our
model
embryogenesis
will
enable
further
exploration
line
other
lineages.
Cell stem cell,
Journal Year:
2023,
Volume and Issue:
30(12), P. 1569 - 1584
Published: Oct. 18, 2023
Studies
of
mammalian
development
have
advanced
our
understanding
the
genetic,
epigenetic,
and
cellular
processes
that
orchestrate
embryogenesis
uncovered
new
insights
into
unique
aspects
human
embryogenesis.
Recent
studies
now
produced
first
epigenetic
maps
early
embryogenesis,
stimulating
ideas
about
reprogramming,
cell
fate
control,
potential
mechanisms
underpinning
developmental
plasticity
in
embryos.
In
this
review,
we
discuss
these
regulation
importance
for
safeguarding
development.
We
also
highlight
unanswered
questions
key
challenges
remain
to
be
addressed.
Cell stem cell,
Journal Year:
2024,
Volume and Issue:
31(3), P. 312 - 333
Published: Feb. 20, 2024
Though
totipotency
and
pluripotency
are
transient
during
early
embryogenesis,
they
establish
the
foundation
for
development
of
all
mammals.
Studying
these
in
vivo
has
been
challenging
due
to
limited
access
ethical
constraints,
particularly
humans.
Recent
progress
led
diverse
culture
adaptations
epiblast
cells
vitro
form
totipotent
pluripotent
stem
cells,
which
not
only
deepen
our
understanding
embryonic
but
also
serve
as
invaluable
resources
animal
reproduction
regenerative
medicine.
This
review
delves
into
hallmarks
shedding
light
on
their
key
molecular
functional
features.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2021,
Volume and Issue:
unknown
Published: May 7, 2021
Summary
Stem
cell-based
embryo
models
offer
unprecedented
experimental
tools
for
studying
early
human
development.
The
usefulness
of
hinges
on
their
molecular,
cellular
and
structural
fidelities
to
in
vivo
counterparts.
To
authenticate
models,
single-cell
RNA-sequencing
has
been
utilised
unbiased
transcriptional
profiling.
However,
a
well-organised
integrated
dataset,
serving
as
universal
reference
benchmarking
remains
unavailable.
Herein,
we
developed
such
reference,
through
integration
six
published
datasets
covering
developmental
stages
from
the
zygote
gastrula.
Lineage
annotations
are
contrasted
validated
with
available
non-human
primate
datasets.
Using
stabilised
UMAP
constructed
web
tool,
where
query
can
be
projected
annotated
predicted
cell
identities.
this
examined
several
recent
highlighting
risk
misannotation
when
relevant
references
lacking.
Nature,
Journal Year:
2023,
Volume and Issue:
626(7998), P. 357 - 366
Published: Dec. 5, 2023
Abstract
Recently,
several
studies
using
cultures
of
human
embryos
together
with
single-cell
RNA-seq
analyses
have
revealed
differences
between
humans
and
mice,
necessitating
the
study
1–8
.
Despite
importance
embryology,
ethical
legal
restrictions
limited
post-implantation-stage
studies.
Thus,
recent
efforts
focused
on
developing
in
vitro
self-organizing
models
stem
cells
9–17
Here,
we
report
genetic
non-genetic
approaches
to
generate
authentic
hypoblast
(naive
hPSC-derived
hypoblast-like
(nHyCs))—known
give
rise
one
two
extraembryonic
tissues
essential
for
embryonic
development—from
naive
pluripotent
(hPSCs).
Our
nHyCs
spontaneously
assemble
hPSCs
form
a
three-dimensional
bilaminar
structure
(bilaminoids)
pro-amniotic-like
cavity.
In
presence
additional
analogues
second
tissue,
trophectoderm,
efficiency
bilaminoid
formation
increases
from
20%
40%,
epiblast
within
bilaminoids
continues
develop
response
trophectoderm-secreted
IL-6.
Furthermore,
show
that
robustly
recapitulate
patterning
anterior–posterior
axis
reflecting
pregastrula
stage,
emergence
which
can
be
shaped
by
genetically
manipulating
DKK1/OTX2
domain.
We
therefore
successfully
modelled
identified
mechanisms
efficiently
guide
stage-specific
growth
progression
as
it
establishes
post-implantation
landmarks
embryogenesis.
Nature,
Journal Year:
2023,
Volume and Issue:
626(7998), P. 367 - 376
Published: Dec. 13, 2023
Abstract
Implantation
of
the
human
embryo
begins
a
critical
developmental
stage
that
comprises
profound
events
including
axis
formation,
gastrulation
and
emergence
haematopoietic
system
1,2
.
Our
mechanistic
knowledge
this
window
life
remains
limited
due
to
restricted
access
in
vivo
samples
for
both
technical
ethical
reasons
3–5
Stem
cell
models
have
emerged
help
unlock
mysteries
6–16
Here
we
present
genetically
inducible
stem
cell-derived
embryoid
model
early
post-implantation
embryogenesis
captures
reciprocal
codevelopment
embryonic
tissue
extra-embryonic
endoderm
mesoderm
niche
with
haematopoiesis.
This
is
produced
from
induced
pluripotent
cells
shows
unanticipated
self-organizing
cellular
programmes
similar
those
occur
embryogenesis,
formation
amniotic
cavity
bilaminar
disc
morphologies
as
well
generation
an
anterior
hypoblast
pole
posterior
domain.
The
layer
these
embryoids
lacks
trophoblast
advanced
multilineage
yolk
sac
tissue-like
morphogenesis
harbours
process
distinct
waves
haematopoiesis,
erythroid-,
megakaryocyte-,
myeloid-
lymphoid-like
cells.
presents
easy-to-use,
high-throughput,
reproducible
scalable
platform
probe
multifaceted
aspects
development
blood
at
stage.
It
will
provide
tractable
human-based
drug
testing
disease
modelling.
Developmental Cell,
Journal Year:
2024,
Volume and Issue:
59(12), P. 1489 - 1505.e14
Published: April 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.
Nature Methods,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 14, 2024
Stem
cell-based
embryo
models
offer
unprecedented
experimental
tools
for
studying
early
human
development.
The
usefulness
of
hinges
on
their
molecular,
cellular
and
structural
fidelities
to
in
vivo
counterparts.
To
authenticate
models,
single-cell
RNA
sequencing
has
been
utilized
unbiased
transcriptional
profiling.
However,
an
organized
integrated
RNA-sequencing
dataset,
serving
as
a
universal
reference
benchmarking
remains
unavailable.
Here
we
developed
such
through
the
integration
six
published
datasets
covering
development
from
zygote
gastrula.
Lineage
annotations
are
contrasted
validated
with
available
nonhuman
primate
datasets.
Using
stabilized
Uniform
Manifold
Approximation
Projection,
constructed
embryogenesis
prediction
tool,
where
query
can
be
projected
annotated
predicted
cell
identities.
this
examined
highlighting
risk
misannotation
when
relevant
references
not
authentication.
Developmental Biology,
Journal Year:
2024,
Volume and Issue:
509, P. 43 - 50
Published: Feb. 5, 2024
Understanding
the
processes
and
mechanisms
underlying
early
human
embryo
development
has
become
an
increasingly
active
important
area
of
research.
It
potential
for
insights
into
clinical
issues
such
as
pregnancy
loss,
origins
congenital
anomalies
developmental
adult
disease,
well
fundamental
biology.
Improved
culture
systems
preimplantation
embryos,
combined
with
new
tools
single
cell
genomics
live
imaging,
are
providing
similarities
differences
between
mouse
development.
However,
access
to
material
is
still
restricted
extended
embryos
regulatory
ethical
concerns.
Stem
cell-derived
models
different
phases
can
potentially
overcome
these
limitations
provide
a
scalable
source
explore
postimplantation
stages
To
date,
clearly
incomplete
replicas
normal
but
future
technological
improvements
be
envisaged.
The
environment
studies
remains
fully
resolved.
