Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 12, 2024
Abstract
During
human
pregnancy,
extravillous
trophoblasts
play
crucial
roles
in
placental
invasion
into
the
maternal
decidua
and
spiral
artery
remodeling.
However,
regulatory
factors
their
action
mechanisms
modulating
trophoblast
specification
have
been
unknown.
By
analyzing
dynamic
changes
transcriptome
enhancer
profile
during
stem
cell
to
differentiation,
we
define
stage-specific
regulators,
including
an
early-stage
transcription
factor,
TFAP2C,
multiple
late-stage
factors.
Loss-of-function
studies
confirm
requirement
of
all
identified
for
adequate
reveal
that
levels
TFAP2C
are
essential.
Notably,
pre-occupies
elements
inactive
trophoblast-active
genes
early
stage
directly
activate
genes,
themselves
as
differentiation
further
progresses,
suggesting
sequential
actions
assuring
differentiation.
Our
results
inter-connected
providing
a
framework
understanding
placentation
placenta-related
complications.
Frontiers in Cell and Developmental Biology,
Journal Year:
2022,
Volume and Issue:
10
Published: Aug. 26, 2022
Lactate,
the
end
product
of
glycolysis,
efficiently
functions
as
carbon
source,
signaling
molecules
and
immune
regulators.
Lactylation,
being
regulated
by
lactate,
has
recently
been
confirmed
a
novel
contributor
to
epigenetic
landscape,
not
only
opening
new
era
for
in-depth
exploration
lactate
metabolism
but
also
offering
key
breakpoints
further
functional
mechanistic
research.
Several
studies
have
identified
pivotal
role
protein
lactylation
in
cell
fate
determination,
embryonic
development,
inflammation,
cancer,
neuropsychiatric
disorders.
This
review
summarized
recent
advances
with
respect
discovery,
derivation,
cross-species
diverse
lactylation.
Further,
we
thoroughly
discussed
discrepancies
limitations
available
studies,
providing
optimal
perspectives
future
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: July 13, 2022
Non-human
primates
are
attractive
laboratory
animal
models
that
accurately
reflect
both
developmental
and
pathological
features
of
humans.
Here
we
present
a
compendium
cell
types
across
multiple
organs
in
cynomolgus
monkeys
(Macaca
fascicularis)
using
single-cell
chromatin
accessibility
RNA
sequencing
data.
The
integrated
map
enables
in-depth
dissection
comparison
molecular
dynamics,
cell-type
compositions
cellular
heterogeneity
tissues
organs.
Using
transcriptomic
data,
infer
pseudotime
trajectories
cell-cell
communications
to
uncover
key
signatures
underlying
their
processes.
Furthermore,
identify
various
cell-specific
cis-regulatory
elements
construct
organ-specific
gene
regulatory
networks
at
the
level.
Finally,
perform
comparative
analyses
landscapes
among
mouse,
monkey
human.
We
show
has
strikingly
higher
degree
similarities
terms
immune-associated
expression
patterns
human
than
mouse.
Taken
together,
our
study
provides
valuable
resource
for
non-human
primate
biology.
Nature Cell Biology,
Journal Year:
2023,
Volume and Issue:
25(8), P. 1185 - 1195
Published: July 24, 2023
Abstract
During
development,
progenitors
simultaneously
activate
one
lineage
while
silencing
another,
a
feature
highly
regulated
in
adult
stem
cells
but
derailed
cancers.
Equipped
to
bind
cognate
motifs
closed
chromatin,
pioneer
factors
operate
at
these
crossroads,
how
they
perform
fate
switching
remains
elusive.
Here
we
tackle
this
question
with
SOX9,
master
regulator
that
diverts
embryonic
epidermal
(EpdSCs)
into
becoming
hair
follicle
cells.
By
engineering
mice
re-activate
SOX9
EpdSCs,
trigger
switching.
Combining
epigenetic,
proteomic
and
functional
analyses,
interrogate
the
ensuing
chromatin
transcriptional
dynamics,
slowed
temporally
by
mature
EpdSC
niche
microenvironment.
We
show
as
binds
opens
key
enhancers
de
novo
it
recruits
co-factors
away
from
enhancers,
which
are
silenced.
Unhinged
its
normal
regulation,
sustained
subsequently
activates
oncogenic
regulators
chart
path
cancers
typified
constitutive
expression.
Journal of Biological Engineering,
Journal Year:
2023,
Volume and Issue:
17(1)
Published: March 2, 2023
Epithelial-mesenchymal
plasticity
(EMP)
involves
bidirectional
transitions
between
epithelial,
mesenchymal
and
multiple
intermediary
hybrid
epithelial/mesenchymal
phenotypes.
While
the
process
of
epithelial-mesenchymal
transition
(EMT)
its
associated
transcription
factors
are
well-characterised,
that
promote
mesenchymal-epithelial
(MET)
stabilise
E/M
phenotypes
less
well
understood.Here,
we
analyse
publicly-available
transcriptomic
datasets
at
bulk
single-cell
level
pinpoint
ELF3
as
a
factor
is
strongly
with
an
epithelial
phenotype
inhibited
during
EMT.
Using
mechanism-based
mathematical
modelling,
also
show
inhibits
progression
This
behaviour
was
observed
in
presence
EMT
inducing
WT1.
Our
model
predicts
MET
induction
capacity
stronger
than
KLF4,
but
weaker
GRHL2.
Finally,
levels
correlates
worse
patient
survival
subset
solid
tumour
types.ELF3
shown
to
be
found
inhibit
complete
suggesting
may
able
counteract
induction,
including
EMT-inducing
factors,
such
The
analysis
data
indicates
prognostic
specific
cell-of-origin
or
lineage.
