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.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2021,
Номер
unknown
Опубликована: Май 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.
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.