Cell stem cell,
Год журнала:
2022,
Номер
29(9), С. 1346 - 1365.e10
Опубликована: Сен. 1, 2022
A
hallmark
of
primate
postimplantation
embryogenesis
is
the
specification
extraembryonic
mesoderm
(EXM)
before
gastrulation,
in
contrast
to
rodents
where
this
tissue
formed
only
after
gastrulation.
Here,
we
discover
that
naive
human
pluripotent
stem
cells
(hPSCs)
are
competent
differentiate
into
EXM
(EXMCs).
EXMCs
specified
by
inhibition
Nodal
signaling
and
GSK3B,
maintained
mTOR
BMP4
activity,
their
transcriptome
epigenome
closely
resemble
monkey
embryo
EXM.
mesenchymal,
can
arise
from
an
epiblast
intermediate,
capable
self-renewal.
Thus,
arising
via
primate-specific
between
implantation
gastrulation
be
modeled
vitro.
We
also
find
most
rare
off-target
within
blastoids
triple
(Kagawa
et
al.,
2021)
correspond
EXMCs.
Our
study
impacts
our
ability
model
molecular
mechanisms
early
related
defects.
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
Cell stem cell,
Год журнала:
2021,
Номер
28(6), С. 1016 - 1022.e4
Опубликована: Май 5, 2021
Human
naive
pluripotent
cells
can
differentiate
into
extraembryonic
trophectoderm
and
hypoblast.
Here
we
describe
a
human
embryo
model
(blastoid)
generated
by
self-organization.
Brief
induction
of
leads
to
formation
blastocyst-like
structures
within
3
days.
Blastoids
are
composed
three
tissue
layers
displaying
exclusive
lineage
markers,
mimicking
the
natural
blastocyst.
Single-cell
transcriptome
analyses
confirm
segregation
trophectoderm,
hypoblast,
epiblast
with
high
fidelity
embryo.
This
versatile
scalable
system
provides
robust
experimental
for
research.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Сен. 21, 2021
Abstract
Understanding
human
development
is
of
fundamental
biological
and
clinical
importance.
Despite
its
significance,
mechanisms
behind
embryogenesis
remain
largely
unknown.
Here,
we
attempt
to
model
early
embryo
with
expanded
pluripotent
stem
cells
(EPSCs)
in
3-dimensions.
We
define
a
protocol
that
allows
us
generate
self-organizing
cystic
structures
from
EPSCs
display
some
hallmarks
embryogenesis.
These
mimic
polarization
cavitation
characteristic
pre-implantation
leading
blastocyst
morphology
formation
the
transition
post-implantation-like
organization
upon
extended
culture.
Single-cell
RNA
sequencing
these
reveals
subsets
bearing
resemblance
epiblast,
hypoblast
trophectoderm
lineages.
Nevertheless,
significant
divergences
natural
blastocysts
persist
key
markers,
signalling
pathways
point
towards
ways
which
transcriptional-level
cell
identities
may
diverge
models
embryo.
Thus,
this
platform
provides
insights
into
design
Seminars in Cell and Developmental Biology,
Год журнала:
2022,
Номер
131, С. 66 - 77
Опубликована: Апрель 4, 2022
The
placenta
is
a
transient
fetal
organ
that
plays
critical
role
in
the
health
and
wellbeing
of
both
fetus
its
mother.
Functionally,
sustains
growth
as
it
facilitates
delivery
oxygen
nutrients
removal
waste
products.
Not
surprisingly,
defective
early
placental
development
primary
cause
common
disorders
pregnancy,
including
recurrent
miscarriage,
restriction,
pre-eclampsia
stillbirth.
Adverse
pregnancy
conditions
will
also
affect
life-long
via
developmental
programming[1].
Despite
importance
reproductive
success
health,
our
understanding
not
extensive,
largely
due
to
ethical
limitations
studying
or
chronological
development,
lack
long-term
vitro
models,
comparative
animal
models.
In
this
review,
we
examine
current
knowledge
human
discuss
maternal
endometrium
fetal-maternal
dialogue
success,
explore
latest
models
trophoblast
endometrial
stem
cells.
addition,
formation
function,
how
nutrient
mediated
during
periods
histotrophic
nutrition
(uptake
uterine
secretions)
haemotrophic
(exchange
between
circulations),
endocrine
function
development.
Abstract
Human
blastocysts
are
comprised
of
the
first
three
cell
lineages
embryo:
trophectoderm,
epiblast
and
primitive
endoderm,
all
which
essential
for
early
development
organ
formation.
However,
due
to
ethical
concerns
restricted
access
human
blastocysts,
a
comprehensive
understanding
embryogenesis
is
still
lacking.
To
bridge
this
knowledge
gap,
reliable
model
system
that
recapitulates
stages
needed.
Here
we
developed
three-dimensional
(3D),
two-step
induction
protocol
generating
blastocyst-like
structures
(EPS-blastoids)
from
extended
pluripotent
stem
(EPS)
cells.
Morphological
single-cell
transcriptomic
analyses
revealed
EPS-blastoids
contain
key
transcriptionally
similar
blastocysts.
Furthermore,
with
embryos
were
cultured
8
or
10
days
in
vitro,
terms
embryonic
structures,
profiles.
In
conclusion,
scalable
mimic
blastocyst
development,
can
potentially
facilitate
study
implantation
failure
induced
by
developmental
defects
at
stage.
