Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Ноя. 23, 2022
Abstract
The
human
genome
contains
more
than
4.5
million
inserts
derived
from
transposable
elements
(TEs),
the
result
of
recurrent
waves
invasion
and
internal
propagation
throughout
evolution.
For
new
TE
copies
to
be
inherited,
they
must
become
integrated
in
germline
or
pre-implantation
embryo,
which
requires
that
their
source
expressed
at
these
stages.
Accordingly,
many
TEs
harbor
DNA
binding
sites
for
pluripotency
factors
OCT4,
NANOG,
SOX2,
KLFs
are
transiently
during
embryonic
activation.
Here,
we
describe
how
primate-restricted
have
additional
lineage-specific
transcription
driving
expression
gastrulation
later
steps
fetal
development.
These
integrants
serve
as
enhancers
fostering
transcription,
amongst
other
targets,
KRAB-zinc
finger
proteins
(KZFPs)
comparable
evolutionary
age,
turn
corral
activity
TE-embedded
regulatory
sequences
a
similarly
lineage-restricted
fashion.
Thus,
KZFP
controllers
play
broad
roles
shaping
transcriptional
networks
early
Nature,
Год журнала:
2021,
Номер
601(7894), С. 600 - 605
Опубликована: Дек. 2, 2021
Abstract
One
week
after
fertilization,
human
embryos
implant
into
the
uterus.
This
event
requires
embryo
to
form
a
blastocyst
consisting
of
sphere
encircling
cavity
lodging
proper.
Stem
cells
can
model
that
we
called
blastoid
1
.
Here
show
naive
pluripotent
stem
cultured
in
PXGL
medium
2
and
triply
inhibited
for
Hippo,
TGF-β
ERK
pathways
efficiently
(with
more
than
70%
efficiency)
blastoids
generating
blastocyst-stage
analogues
three
founding
lineages
(more
97%
trophectoderm,
epiblast
primitive
endoderm)
according
sequence
timing
development.
Blastoids
spontaneously
first
axis,
observe
induces
local
maturation
polar
thereby
endowing
with
capacity
directionally
attach
hormonally
stimulated
endometrial
cells,
as
during
implantation.
Thus,
propose
such
is
faithful,
scalable
ethical
investigating
implantation
development
3,4
Nature,
Год журнала:
2023,
Номер
622(7983), С. 584 - 593
Опубликована: Июнь 27, 2023
Abstract
The
human
embryo
undergoes
morphogenetic
transformations
following
implantation
into
the
uterus,
but
our
knowledge
of
this
crucial
stage
is
limited
by
inability
to
observe
in
vivo.
Models
derived
from
stem
cells
are
important
tools
for
interrogating
developmental
events
and
tissue–tissue
crosstalk
during
these
stages
1
.
Here
we
establish
a
model
post-implantation
embryo,
embryoid,
comprising
embryonic
extraembryonic
tissues.
We
combine
two
types
extraembryonic-like
cell
generated
overexpression
transcription
factors
with
wild-type
promote
their
self-organization
structures
that
mimic
several
aspects
embryo.
These
self-organized
aggregates
contain
pluripotent
epiblast-like
domain
surrounded
Our
functional
studies
demonstrate
robustly
differentiates
amnion,
mesenchyme
primordial
germ
cell-like
response
bone
protein
cues.
In
addition,
identify
an
inhibitory
role
SOX17
specification
anterior
hypoblast-like
2
Modulation
subpopulations
compartment
demonstrates
influence
differentiation,
highlighting
crosstalk.
conclusion,
present
modular,
tractable,
integrated
3
will
enable
us
probe
key
questions
development,
critical
window
which
substantial
numbers
pregnancies
fail.
The
ability
to
study
human
post-implantation
development
remains
limited
owing
ethical
and
technical
challenges
associated
with
intrauterine
after
implantation1.
Embryo-like
models
spatially
organized
morphogenesis
structure
of
all
defining
embryonic
extra-embryonic
tissues
the
conceptus
(that
is,
disc,
bilaminar
yolk
sac,
chorionic
sac
surrounding
trophoblast
layer)
remain
lacking1,2.
Mouse
naive
stem
cells
have
recently
been
shown
give
rise
capable
self-assembling
into
post-gastrulation
structured
stem-cell-based
embryo
(called
SEMs)3.
Here
we
extend
those
findings
humans
using
only
genetically
unmodified
(cultured
in
enhanced
cell
medium
conditions)4.
Such
fully
integrated
complete
SEMs
recapitulate
organization
nearly
known
lineages
compartments
embryos,
including
epiblast,
hypoblast,
mesoderm
layer
latter
compartments.
These
demonstrated
developmental
growth
dynamics
that
resemble
key
hallmarks
stage
embryogenesis
up
13-14
days
fertilization
(Carnegie
6a).
include
disc
formation,
epiblast
lumenogenesis,
polarized
amniogenesis,
anterior-posterior
symmetry
breaking,
primordial
germ-cell
specification,
visceral
parietal
endoderm
expansion
defines
a
cavity
connecting
stalk,
trophoblast-surrounding
compartment
demonstrating
syncytium
lacunae
formation.
This
SEM
platform
will
probably
enable
experimental
investigation
previously
inaccessible
windows
early
post
implantation
peri-gastrulation
development.
Nature,
Год журнала:
2023,
Номер
622(7983), С. 574 - 583
Опубликована: Июнь 27, 2023
Abstract
Investigating
human
development
is
a
substantial
scientific
challenge
due
to
the
technical
and
ethical
limitations
of
working
with
embryonic
samples.
In
face
these
difficulties,
stem
cells
have
provided
an
alternative
experimentally
model
inaccessible
stages
in
vitro
1–13
.
Here
we
show
that
pluripotent
can
be
triggered
self-organize
into
three-dimensional
structures
recapitulate
some
key
spatiotemporal
events
early
post-implantation
development.
Our
system
reproducibly
captures
spontaneous
differentiation
co-development
epiblast-like
extra-embryonic
hypoblast-like
lineages,
establishes
signalling
hubs
secreted
modulators
undergoes
symmetry
breaking-like
events.
Single-cell
transcriptomics
confirms
diverse
cell
states
perigastrulating
embryo
14,15
without
establishing
placental
types,
including
signatures
epiblast,
amniotic
ectoderm,
primitive
streak,
mesoderm,
endoderm,
as
well
initial
yolk
sac
induction.
Collectively,
our
features
spanning
from
Carnegie
stage
16
4–7,
offering
reproducible,
tractable
scalable
experimental
platform
understand
basic
cellular
molecular
mechanisms
underlie
development,
new
opportunities
dissect
congenital
pathologies
high
throughput.
Cell stem cell,
Год журнала:
2022,
Номер
29(5), С. 744 - 759.e6
Опубликована: Апрель 18, 2022
In
primates,
the
amnion
emerges
through
cavitation
of
epiblast
during
implantation,
whereas
in
other
species
it
does
so
later
at
gastrulation
by
folding
ectoderm.
How
mechanisms
amniogenesis
diversified
evolution
remains
unknown.
Unexpectedly,
single-cell
analysis
primate
embryos
uncovered
two
transcriptionally
and
temporally
distinct
waves.
To
study
this,
we
employed
naive-to-primed
transition
human
pluripotent
stem
cells
(hPSCs)
to
model
peri-implantation
development.
Partially
primed
hPSCs
transiently
gained
ability
differentiate
into
cavitating
epithelium
that
morphologically
matched
early
amnion,
fully
produced
resembling
late
instead,
thus
recapitulating
independent
differentiation
The
wave
follows
a
trophectoderm-like
pathway
encompasses
cavitation,
resembles
an
ectoderm-like
route
gastrulation.
discovery
waves
explains
how
could
emerge
via
duplication
pre-existing
trophectoderm
program.
