Three‐dimensional stem cell models of mammalian gastrulation
BioEssays,
Год журнала:
2024,
Номер
46(12)
Опубликована: Авг. 28, 2024
Abstract
Gastrulation
is
a
key
milestone
in
the
development
of
an
organism.
It
period
cell
proliferation
and
coordinated
cellular
rearrangement,
that
creates
outline
body
plan.
Our
current
understanding
mammalian
gastrulation
has
been
improved
by
embryo
culture,
but
there
are
still
many
open
questions
difficult
to
address
because
intrauterine
embryos
low
number
specimens.
In
case
humans,
additional
difficulties
associated
with
technical
ethical
challenges.
Over
last
few
years,
pluripotent
stem
models
being
developed
have
potential
become
useful
tools
understand
gastrulation.
Here
we
review
these
special
emphasis
on
gastruloids
provide
survey
methods
produce
them
robustly,
their
uses,
relationship
embryos,
prospects
as
well
limitations.
Язык: Английский
Stem cell culture conditions affect in vitro differentiation potential and mouse gastruloid formation
PLoS ONE,
Год журнала:
2025,
Номер
20(3), С. e0317309 - e0317309
Опубликована: Март 26, 2025
Aggregating
low
numbers
of
mouse
embryonic
stem
cells
(mESCs)
and
inducing
Wnt
signalling
generates
‘gastruloids’,
self-organising
complex
structures
that
display
an
anteroposterior
organisation
cell
types
derived
from
all
three
germ
layers.
Current
gastruloid
protocols
considerable
heterogeneity
between
experiments
in
terms
morphology,
elongation
efficiency,
type
composition.
We
therefore
investigated
whether
altering
the
mESC
pluripotency
state
would
provide
more
consistent
results.
By
growing
lines
two
different
genetic
backgrounds
intervals
ESLIF
2i
medium
was
modulated,
culture
as
well
resulting
gastruloids
were
analysed.
Microscopic
analysis
showed
a
pre-culture-specific
effect
on
formation,
aspect
ratio
reproducibility.
RNA-seq
start
population
confirmed
short-term
pulses
modulate
state,
result
cellular
states.
Since
multiple
epigenetic
regulators
detected
among
top
differentially
expressed
genes,
we
further
analysed
genome-wide
DNA
methylation
H3K27me3
distributions.
observed
differences
conditions,
most
dominantly
promoter
regions
developmental
regulators.
Lastly,
when
composition
grown
these
pre-cultures,
mESCs
subjected
to
2i-ESLIF
preceding
aggregation
generated
consistently,
including
mesodermal
contributions
compared
ESLIF-only
control.
These
results
indicate
optimisation
allows
modulation
differentiation
during
formation.
Язык: Английский
Progress in understanding the vertebrate segmentation clock
Nature Reviews Genetics,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 4, 2025
Язык: Английский
Exploring the Effects of Changes in Dietary Protein Content on Naturally Aging Mice Based on Comprehensive Quantitative Scoring and Metabolomic Analysis
Nutrients,
Год журнала:
2025,
Номер
17(9), С. 1542 - 1542
Опубликована: Апрель 30, 2025
During
aging,
protein
nutrition
has
a
bidirectional
role
in
regulating
healthy
lifespan
by
modulating
body
metabolism
and
neurological
function.
However,
the
current
"low-high"
hypothesis
on
dynamics
of
requirements
is
mainly
based
male
animal
models,
its
applicability
to
female
physiology
(e.g.,
estrogen
fluctuations)
unclear.
The
present
study
aims
fill
gap
demand
naturally
aging
mice
investigate
effects
different
levels
health
status
C57BL/6J
at
stages
aging.
In
this
study,
four
dietary
interventions
(high
protein,
HP;
low
LP;
model
test,
MT;
control,
C)
were
evaluated
constructing
mouse
three
ages,
9
M
(9
months),
16
(16
20
(20
which
are
approximately
equivalent
34,
65,
78
years
age
humans,
respectively,
determine
mice.
quantitatively
described
behavioral,
neuropathological,
oxidative,
inflammatory
indices
NMR
metabolomics
using
Principal
Component
Analysis
construct
comprehensive
quantitative
scoring
method.
scores
Fsum
was
highest
HP
group,
lowest
LP
between
MT
group.
intervention
showed
most
significant
improvement
aged
group
M)
mice,
with
35.2%
reduction
avoidance
latency
(p
<
0.01)
32.9%
increase
pyramidal
cell
density
hippocampal
CA1
region
0.05),
while
led
cognitive
decline
an
that
prolonged
15.2%
0.05).
Metabolomics
analysis
revealed
samples
all
ages
age-dependent
metabolic
re-adaptation:
may
reflect
gut
microbial
rather
than
direct
host
TCA
cycle
activity,
suggesting
indirect
association
energy
metabolism;
enhanced
degradation
branched-chain
amino
acids
(BCAAs)
seen
middle-aged
M);
acid
biosynthesis
predominant
old
M).
Female
have
sustained
neuromotor
benefits
high-protein
diets
stages,
their
differ
significantly
from
those
males.
reveals
critical
gender
factors
nutritional
strategies
provides
experimental
basis
for
precise
supplementation
older
women.
Язык: Английский
The proteomic landscape and temporal dynamics of mammalian gastruloid development
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 7, 2024
Gastrulation
is
the
highly
coordinated
process
by
which
early
embryo
breaks
symmetry,
establishes
germ
layers
and
a
body
plan,
sets
stage
for
organogenesis.
As
mammalian
development
challenging
to
study
Язык: Английский
Exome-wide analysis of congenital kidney anomalies reveals new genes and shared architecture with developmental disorders
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 6, 2024
Abstract
Kidney
anomalies
(KA)
are
developmental
disorders
that
commonly
cause
pediatric
chronic
kidney
disease
and
mortality.
We
examined
rare
coding
variants
in
248
KA
trios
1,742
singleton
cases
compared
them
to
22,258
controls.
Diagnostic
candidate
diagnostic
were
detected
14.1%
of
cases.
a
significant
enrichment
damaging
constrained
genes
expressed
during
development
associated
with
other
disorders,
suggesting
phenotype
expansion.
Consistent
these
data,
18%
patients
had
neurodevelopmental
or
cardiac
phenotypes.
Extrarenal
phenotypes
higher
burden
variants.
Statistical
analyses
identified
40
novel
genes,
2
which
confirmed
as
new
genes:
ARID3A
NR6A1.
This
study
suggests
many
yet-unidentified
syndromes
would
be
discoverable
larger
cohorts
cross-phenotype
analysis,
leading
clarification
the
genetic
phenotypic
spectrum
disorders.
Язык: Английский