Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling
Cell stem cell,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 1, 2025
Metabolic
pathways
can
influence
cell
fate
decisions,
yet
their
regulative
role
during
embryonic
development
remains
poorly
understood.
Here,
we
demonstrate
an
instructive
of
glycolytic
activity
in
regulating
signaling
involved
mesoderm
and
endoderm
specification.
Using
a
mouse
stem
(mESC)-based
vitro
model
for
gastrulation,
found
that
glycolysis
inhibition
increases
ectodermal
fates
at
the
expense
mesodermal
endodermal
lineages.
We
this
relationship
is
dose
dependent,
enabling
metabolic
control
germ
layer
proportions
through
exogenous
glucose
levels.
further
show
acts
as
upstream
regulator
Nodal
Wnt
its
on
specification
be
decoupled
from
effects
growth.
Finally,
confirm
generality
our
findings
using
human
gastrulation
model.
Our
work
underscores
dependence
conditions
provides
mechanistic
insight
into
nutritional
regulation
decision-making.
Language: Английский
Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids
Kyoung Jo,
No information about this author
Zong-Yuan Liu,
No information about this author
Gauri Patel
No information about this author
et al.
Published: July 11, 2024
The
role
of
FGF
is
the
least
understood
morphogens
driving
mammalian
gastrulation.
Here
we
investigated
function
in
a
stem
cell
model
for
human
gastrulation
known
as
2D
gastruloid.
We
found
ring
FGF-dependent
ERK
activity
that
closely
follows
emergence
primitive
streak
(PS)-like
cells
but
expands
further
inward.
showed
this
pattern
required
PS-like
differentiation
and
loss
upon
receptor
inhibition
can
be
rescued
by
directly
activating
ERK.
demonstrated
ERK-ring
depends
on
localized
activation
basally
receptors
(FGFR)
endogenous
gradients.
confirm
extend
previous
studies
analyzing
expression
pathway
components,
showing
main
to
FGFR1
key
ligands
FGF2/4/17,
similar
monkey
embryo
different
from
mouse.
In
situ
hybridization
scRNA-seq
revealed
Language: Английский
Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids
Kyoung Jo,
No information about this author
Zong-Yuan Liu,
No information about this author
Gauri Patel
No information about this author
et al.
Published: Nov. 8, 2024
The
role
of
FGF
is
the
least
understood
morphogens
driving
mammalian
gastrulation.
Here
we
investigated
function
in
a
stem
cell
model
for
human
gastrulation
known
as
2D
gastruloid.
We
found
ring
FGF-dependent
ERK
activity
that
closely
follows
emergence
primitive
streak
(PS)-like
cells
but
expands
further
inward.
showed
this
pattern
required
PS-like
differentiation
and
loss
upon
receptor
inhibition
can
be
rescued
by
directly
activating
ERK.
demonstrated
ERK-ring
depends
on
localized
activation
basally
receptors
(FGFR)
endogenous
gradients.
confirm
extend
previous
studies
analyzing
expression
pathway
components,
showing
main
to
FGFR1
key
ligands
FGF2/4/17,
similar
monkey
embryo
different
from
mouse.
In
situ
hybridization
scRNA-seq
revealed
FGF4
FGF17
colocalize
with
PS
marker
TBXT
only
maintained
nascent
mesoderm
endoderm.
reduction
both
reduced
their
derivatives,
indicating
overlapping
function.
Thus,
have
identified
previously
unknown
signaling
gastruloids
possibly
embryo,
driven
mechanism
where
signal
through
induce
cells.
Language: Английский
Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids
Kyoung Jo,
No information about this author
Zong-Yuan Liu,
No information about this author
Gauri Patel
No information about this author
et al.
Published: Nov. 8, 2024
The
role
of
FGF
is
the
least
understood
morphogens
driving
mammalian
gastrulation.
Here
we
investigated
function
in
a
stem
cell
model
for
human
gastrulation
known
as
2D
gastruloid.
We
found
ring
FGF-dependent
ERK
activity
that
closely
follows
emergence
primitive
streak
(PS)-like
cells
but
expands
further
inward.
showed
this
pattern
required
PS-like
differentiation
and
loss
upon
receptor
inhibition
can
be
rescued
by
directly
activating
ERK.
demonstrated
ERK-ring
depends
on
localized
activation
basally
receptors
(FGFR)
endogenous
gradients.
confirm
extend
previous
studies
analyzing
expression
pathway
components,
showing
main
to
FGFR1
key
ligands
FGF2/4/17,
similar
monkey
embryo
different
from
mouse.
In
situ
hybridization
scRNA-seq
revealed
FGF4
FGF17
colocalize
with
PS
marker
TBXT
only
maintained
nascent
mesoderm
endoderm.
reduction
both
reduced
their
derivatives,
indicating
overlapping
function.
Thus,
have
identified
previously
unknown
signaling
gastruloids
possibly
embryo,
driven
mechanism
where
signal
through
induce
cells.
Language: Английский