Biology,
Год журнала:
2024,
Номер
13(2), С. 71 - 71
Опубликована: Янв. 24, 2024
Mouse
zygotes
undergo
multiple
rounds
of
cell
division,
resulting
in
the
formation
preimplantation
blastocysts
comprising
three
lineages:
trophectoderm
(TE),
epiblast
(EPI),
and
primitive
endoderm
(PrE).
Cell
fate
determination
plays
a
crucial
role
establishing
healthy
pregnancy.
The
initial
separation
lineages
gives
rise
to
TE
inner
mass
(ICM),
from
which
trophoblast
stem
cells
(TSC)
embryonic
(ESC)
can
be
derived
vitro.
Studying
lineage
differentiation
is
greatly
facilitated
by
clear
functional
distinction
between
TSC
ESC.
However,
transitioning
these
two
types
naturally
poses
challenges.
In
this
study,
we
demonstrate
that
inhibiting
LATS
kinase
promotes
conversion
ICM
also
effectively
reprograms
ESC
into
stable,
self-renewing
TS-like
(TSLC).
Compared
TSC,
TSLC
exhibits
similar
molecular
properties,
including
high
expression
marker
genes
such
as
Cdx2,
Eomes,
Tfap2c,
well
hypomethylation
their
promoters.
Importantly,
not
only
displays
ability
differentiate
mature
vitro
but
participates
placenta
vivo.
These
findings
highlight
efficient
reprogramming
ESCs
TSLCs
using
small
inducer,
provides
new
reference
for
understanding
regulatory
network
TSCs.
The
lineage
decision
that
generates
the
epiblast
and
primitive
endoderm
from
inner
cell
mass
(ICM)
is
a
paradigm
for
fate
specification.
Recent
mathematics
has
formalized
Waddington's
landscape
metaphor
proven
decisions
in
detailed
gene
network
models
must
conform
to
small
list
of
low-dimensional
stereotypic
changes
called
bifurcations.
most
plausible
bifurcation
ICM
so-called
heteroclinic
flip
we
define
elaborate
here.
Our
re-analysis
recent
data
suggests
there
sufficient
movement
so
FGF
signal,
which
drives
decision,
can
be
treated
as
spatially
uniform.
We
thus
extend
model
single
entire
by
means
self-consistently
defined
time-dependent
signal.
This
consistent
with
available
propose
additional
dynamic
experiments
test
it
further.
demonstrates
simplified,
quantitative
intuitively
transparent
descriptions
are
possible
when
attention
shifted
specific
genes
lineages.
very
any
situation
where
embryo
needs
control
over
relative
proportions
two
fates
morphogen
feedback.
ABSTRACT
The
extracellular
signal-regulated
kinase
(ERK)
pathway
governs
cell
proliferation,
differentiation
and
migration,
therefore
plays
key
roles
in
various
developmental
regenerative
processes.
Recent
advances
genetically
encoded
fluorescent
biosensors
have
unveiled
hitherto
unrecognized
ERK
activation
dynamics
space
time
their
functional
importance
mainly
cultured
cells.
However,
during
embryonic
development
still
only
been
visualized
limited
numbers
of
model
organisms,
we
are
far
from
a
sufficient
understanding
the
played
by
dynamics.
In
this
Review,
first
provide
an
overview
used
for
visualization
activity
live
Second,
highlight
applications
to
studies
organisms
discuss
current
how
decoded
fate
decision-making.
Development Growth & Differentiation,
Год журнала:
2023,
Номер
65(5), С. 245 - 254
Опубликована: Май 16, 2023
Abstract
Cell
fate
decisions
emerge
as
a
consequence
of
complex
set
gene
regulatory
networks.
Models
these
networks
are
known
to
have
more
parameters
than
data
can
determine.
Recent
work,
inspired
by
Waddington's
metaphor
landscape,
has
instead
tried
understand
the
geometry
Here,
we
describe
recent
results
on
appropriate
mathematical
framework
for
constructing
landscapes.
This
allows
construction
minimally
parameterized
models
consistent
with
cell
behavior.
We
review
existing
examples
where
geometrical
been
used
fit
experimental
and
how
spatial
interactions
between
cells
be
understood
geometrically.
Biology,
Год журнала:
2024,
Номер
13(2), С. 71 - 71
Опубликована: Янв. 24, 2024
Mouse
zygotes
undergo
multiple
rounds
of
cell
division,
resulting
in
the
formation
preimplantation
blastocysts
comprising
three
lineages:
trophectoderm
(TE),
epiblast
(EPI),
and
primitive
endoderm
(PrE).
Cell
fate
determination
plays
a
crucial
role
establishing
healthy
pregnancy.
The
initial
separation
lineages
gives
rise
to
TE
inner
mass
(ICM),
from
which
trophoblast
stem
cells
(TSC)
embryonic
(ESC)
can
be
derived
vitro.
Studying
lineage
differentiation
is
greatly
facilitated
by
clear
functional
distinction
between
TSC
ESC.
However,
transitioning
these
two
types
naturally
poses
challenges.
In
this
study,
we
demonstrate
that
inhibiting
LATS
kinase
promotes
conversion
ICM
also
effectively
reprograms
ESC
into
stable,
self-renewing
TS-like
(TSLC).
Compared
TSC,
TSLC
exhibits
similar
molecular
properties,
including
high
expression
marker
genes
such
as
Cdx2,
Eomes,
Tfap2c,
well
hypomethylation
their
promoters.
Importantly,
not
only
displays
ability
differentiate
mature
vitro
but
participates
placenta
vivo.
These
findings
highlight
efficient
reprogramming
ESCs
TSLCs
using
small
inducer,
provides
new
reference
for
understanding
regulatory
network
TSCs.
