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
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.
Nature,
Год журнала:
2022,
Номер
612(7941), С. 732 - 738
Опубликована: Дек. 14, 2022
Our
understanding
of
human
early
development
is
severely
hampered
by
limited
access
to
embryonic
tissues.
Due
their
close
evolutionary
relationship
with
humans,
nonhuman
primates
are
often
used
as
surrogates
understand
but
currently
suffer
from
a
lack
in
vivo
datasets,
especially
gastrulation
organogenesis
during
which
the
major
cell
types
dynamically
specified.
To
fill
this
gap,
we
collected
six
Carnegie
stage
8-11
cynomolgus
monkey
(Macaca
fascicularis)
embryos
and
performed
in-depth
transcriptomic
analyses
56,636
single
cells.
show
features
perigastrulation
types,
help
shed
light
on
morphogenetic
events
including
primitive
streak
development,
somitogenesis,
gut
tube
formation,
neural
patterning
crest
differentiation
primates.
In
addition,
comparative
mouse
embryoids
uncovered
conserved
divergent
across
species-for
example,
species-specific
dependency
Hippo
signalling
presomitic
mesoderm
differentiation-and
provide
an
initial
assessment
relevant
stem
models
organogenesis.
This
comprehensive
single-cell
transcriptome
atlas
not
only
fills
knowledge
gap
primate
research
field
also
serves
invaluable
resource
for
embryogenesis
developmental
disorders.
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 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
