Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 17, 2024
Abstract
In
contrast
to
rodents,
the
mechanisms
underlying
human
trophectoderm
and
early
placenta
specification
are
understudied
due
ethical
barriers
scarcity
of
embryos.
Recent
reports
have
shown
that
pluripotent
stem
cells
(PSCs)
can
differentiate
into
(TE)-like
(TELCs)
trophoblast
(TSCs),
offering
a
valuable
in
vitro
model
study
specification.
Here,
we
demonstrate
VGLL1
(vestigial-like
family
member
1),
which
is
highly
expressed
during
non-human
primate
TE
vivo
but
negligibly
mouse,
critical
regulator
cell
fate
determination
self-renewal
TELCs
TSCs
derived
from
naïve
PSCs.
Mechanistically,
partners
with
transcription
factor
TEAD4
(TEA
domain
4)
regulate
chromatin
accessibility
at
target
gene
loci
through
histone
acetylation
acts
cooperation
GATA3
TFAP2C.
Our
work
relevant
understand
embryogenesis
how
it
differs
other
mammalian
species.
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(3), P. 113926 - 113926
Published: March 1, 2024
The
Hippo
signaling
pathway
is
a
central
growth
control
mechanism
in
multicellular
organisms.
By
integrating
diverse
mechanical,
biochemical,
and
stress
cues,
the
orchestrates
proliferation,
survival,
differentiation,
mechanics
of
cells,
which
turn
regulate
organ
development,
homeostasis,
regeneration.
A
deep
understanding
regulation
function
therefore
holds
great
promise
for
developing
novel
therapeutics
regenerative
medicine.
Here,
we
provide
updates
on
molecular
organization
mammalian
network,
review
regulatory
signals
functional
outputs
pathway,
discuss
roles
development
Nature Structural & Molecular Biology,
Journal Year:
2023,
Volume and Issue:
30(4), P. 527 - 538
Published: April 1, 2023
The
placenta
is
a
fast-evolving
organ
with
large
morphological
and
histological
differences
across
eutherians,
but
the
genetic
changes
driving
placental
evolution
have
not
been
fully
elucidated.
Transposable
elements,
through
their
capacity
to
quickly
generate
variation
affect
host
gene
regulation,
may
helped
define
species-specific
trophoblast
expression
programs.
Here
we
assess
contribution
of
transposable
elements
human
as
enhancers
or
promoters.
Using
epigenomic
data
from
primary
stem-cell
lines,
identified
multiple
endogenous
retrovirus
families
regulatory
potential
that
lie
close
genes
preferential
in
trophoblast.
These
largely
primate-specific
are
associated
inter-species
bound
by
transcription
factors
key
roles
development.
editing,
demonstrate
several
act
transcriptional
important
genes,
such
CSF1R
PSG5.
We
also
identify
an
LTR10A
element
regulates
ENG
expression,
affecting
secretion
soluble
endoglin,
implications
for
preeclampsia.
Our
show
transposons
made
contributions
suggest
activity
pregnancy
outcomes.
Proceedings of the National Academy of Sciences,
Journal Year:
2020,
Volume and Issue:
117(30), P. 17864 - 17875
Published: July 15, 2020
Significance
Reproductive
success
in
placental
mammals
relies
on
proper
development
of
the
trophoblast
lineage.
In
particular,
a
balance
self-renewal
vs.
differentiation
progenitors
is
critical
for
establishment
pregnancy.
A
defect
this
process
causes
early
pregnancy
loss.
Here,
we
showed
that
Hippo
signaling
effector,
TEAD4,
essential
progenitor
postimplantation
mammalian
embryos.
Using
genetic
mouse
models
and
human
TSCs,
including
TSCs
from
patients
with
recurrent
losses,
identified
TEAD4-dependent,
evolutionarily
conserved
gene
expression
program
promotes
stemness
cell
proliferation
ensures
utero
survival
developing
fetus.
Development,
Journal Year:
2021,
Volume and Issue:
148(21)
Published: Oct. 15, 2021
ABSTRACT
Two
recently
developed
models,
trophoblast
organoids
and
stem
cells
(TSCs),
are
useful
tools
to
further
the
understanding
of
human
placental
development.
Both
differentiate
from
villous
cytotrophoblast
(VCT)
either
extravillous
(EVT)
or
syncytiotrophoblast
(SCT).
Here,
we
compare
transcriptomes
miRNA
profiles
these
models
identify
which
they
resemble
in
vivo.
Our
findings
indicate
that
TSCs
do
not
readily
undergo
SCT
differentiation
closely
at
base
cell
columns
where
EVT
derives.
In
contrast,
similar
VCT
spontaneous
differentiation.
A
defining
feature
is
leukocyte
antigen
(HLA)
null,
whereas
expresses
HLA-C,
-G
-E
molecules.
We
find
retain
vivo
characteristics.
express
classical
HLA-A
HLA-B
molecules,
maintain
their
expression
after
differentiation,
with
upregulation
HLA-G.
Furthermore,
HLA
differs
when
grown
3D
rather
than
2D,
suggesting
mechanical
cues
important.
results
can
be
used
select
most
suitable
model
for
study
development,
function
pathology.
Cellular and Molecular Life Sciences,
Journal Year:
2022,
Volume and Issue:
79(6)
Published: May 13, 2022
Abstract
Correct
development
of
the
human
placenta
and
its
differentiated
epithelial
cells,
syncytial
trophoblasts
(STBs)
extravillous
(EVTs),
is
crucial
for
a
successful
pregnancy
outcome.
STBs
develop
by
cell
fusion
mononuclear
cytotrophoblasts
(CTBs)
in
placental
floating
villi,
whereas
migratory
EVTs
originate
from
specialized
villi
anchoring
to
maternal
decidua.
Defects
trophoblast
differentiation
have
been
associated
with
severe
disorders
such
as
early-onset
preeclampsia
fetal
growth
restriction.
However,
evolutionary
pathways
underlying
normal
adverse
placentation
are
poorly
understood.
Herein,
we
discuss
Wingless
(WNT)
NOTCH
signaling,
two
that
play
pivotal
roles
development.
Whereas
WNT
necessary
expansion
progenitors
stem
NOTCH1
required
proliferation
survival
EVT
precursors.
Differentiation
latter
orchestrated
switch
receptor
expression
well
changes
ligands
their
downstream
effectors.