Biomacromolecules,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 29, 2025
The
field
of
mechanobiology
has
grown
in
the
past
decade,
but
limited
studies
investigate
how
extracellular
matrix
affects
cell
metabolome.
methionine
cycle
involves
catabolism
and
regeneration
through
donation
recovery
a
single
methyl
group;
this
group
can
methylate
DNA,
RNA,
proteins
to
alter
gene
expression
protein-protein
interactions.
Through
studying
cells
cultured
on
fibrous
(mimicking
healthy
matrice
(ECM))
flat
severely
fibrotic
ECM)
substrates,
we
observed
an
increase
enzyme
substrate.
We
also
present
is
modulated
by
ECM
transmembrane
protein
integrin
β1.
By
inhibiting
activation
ligand-mimicking
peptide
RGD,
that
was
protected
from
alteration.
results
presented
provide
insight
into
possible
therapeutic
targets
for
diseases
knowledge
mechanisms
which
alters
processes.
ABSTRACT
In
embryonic
stem
cell
(ESC)
models
for
early
development,
spatially
and
temporally
varying
patterns
of
signaling
types
emerge
spontaneously.
However,
mechanistic
insight
into
this
dynamic
self-organization
is
limited
by
a
lack
methods
spatiotemporal
control
signaling,
the
relevance
signal
dynamics
cell-to-cell
variability
to
pattern
emergence
remains
unknown.
Here,
we
combine
optogenetic
stimulation,
imaging
transcriptomic
approaches
study
human
ESCs
(hESC)
in
two-dimensional
(2D)
culture.
Morphogen
were
controlled
via
activation
canonical
Wnt/β-catenin
(optoWnt),
which
drove
broad
transcriptional
changes
mesendoderm
differentiation
at
high
efficiency
(>99%
cells).
When
activated
within
subpopulations,
optoWnt
induced
distinct
epithelial
mesenchymal
domains,
mediated
migration,
an
mesenchymal-like
transition
TGFβ
signaling.
Furthermore,
demonstrate
that
such
subpopulations
can
be
used
uncover
feedback
mechanisms
between
neighboring
types.
These
findings
reveal
Wnt
sufficient
generate
tissue-scale
patterning
establish
hESC
model
system
investigating
relevant
embryogenesis.
Nature,
Год журнала:
2024,
Номер
632(8027), С. 1073 - 1081
Опубликована: Июль 17, 2024
Measurements
of
gene
expression
or
signal
transduction
activity
are
conventionally
performed
using
methods
that
require
either
the
destruction
live
imaging
a
biological
sample
within
timeframe
interest.
Here
we
demonstrate
an
alternative
paradigm
in
which
such
activities
stably
recorded
to
genome.
Enhancer-driven
genomic
recording
transcriptional
multiplex
(ENGRAM)
is
based
on
signal-dependent
production
prime
editing
guide
RNAs
mediate
insertion
signal-specific
barcodes
(symbols)
into
genomically
encoded
unit.
We
show
how
this
strategy
can
be
used
for
cell-type-specific
dozens
hundreds
cis-regulatory
elements
with
high
fidelity,
sensitivity
and
reproducibility.
Leveraging
pathway-responsive
elements,
also
time-
concentration-dependent
WNT,
NF-κB
Tet-On
activities.
By
coupling
ENGRAM
sequential
genome
via
DNA
Typewriter
Cell,
Год журнала:
2024,
Номер
187(14), С. 3461 - 3495
Опубликована: Июнь 20, 2024
Developmental
biology-the
study
of
the
processes
by
which
cells,
tissues,
and
organisms
develop
change
over
time-has
entered
a
new
golden
age.
After
molecular
genetics
revolution
in
80s
90s
diversification
field
early
21st
century,
we
have
phase
when
powerful
technologies
provide
approaches
open
unexplored
avenues.
Progress
has
been
accelerated
advances
genomics,
imaging,
engineering,
computational
biology
emerging
model
systems
ranging
from
tardigrades
to
organoids.
We
summarize
how
revolutionary
led
remarkable
progress
understanding
animal
development.
describe
classic
questions
gene
regulation,
pattern
formation,
morphogenesis,
organogenesis,
stem
cell
are
being
revisited.
discuss
connections
development
with
evolution,
self-organization,
metabolism,
time,
ecology.
speculate
developmental
might
evolve
an
era
synthetic
biology,
artificial
intelligence,
human
engineering.
Nature Methods,
Год журнала:
2024,
Номер
21(5), С. 798 - 803
Опубликована: Март 20, 2024
Abstract
Multicellular
systems
grow
over
the
course
of
weeks
from
single
cells
to
tissues
or
even
full
organisms,
making
live
imaging
challenging.
To
bridge
spatiotemporal
scales,
we
present
an
open-top
dual-view
and
dual-illumination
light-sheet
microscope
dedicated
large
specimens
at
single-cell
resolution.
The
configuration
objectives
together
with
a
customizable
multiwell
mounting
system
combines
dual
view
high-throughput
multiposition
imaging.
We
use
this
image
wide
variety
samples
highlight
its
capabilities
gain
quantitative
information
in
such
as
mature
intestinal
organoids
gastruloids.
Nature Cell Biology,
Год журнала:
2024,
Номер
26(10), С. 1790 - 1803
Опубликована: Авг. 20, 2024
Abstract
Gastruloids
are
a
powerful
in
vitro
model
of
early
human
development.
However,
although
elongated
and
composed
all
three
germ
layers,
gastruloids
do
not
morphologically
resemble
post-implantation
embryos.
Here
we
show
that
an
pulse
retinoic
acid
(RA),
together
with
later
Matrigel,
robustly
induces
posterior
embryo-like
morphological
structures,
including
neural
tube
flanked
by
segmented
somites
diverse
cell
types,
crest,
progenitors,
renal
progenitors
myocytes.
Through
silico
staging
based
on
single-cell
RNA
sequencing,
find
RA-gastruloids
progress
further
than
other
or
mouse
embryo
models,
aligning
to
E9.5
CS11
cynomolgus
monkey
We
leverage
chemical
genetic
perturbations
confirm
WNT
BMP
signalling
regulate
somite
formation
length
the
context,
while
transcription
factors
TBX6
PAX3
underpin
presomitic
mesoderm
respectively.
Looking
forward,
robust,
scalable
for
decoding
embryogenesis.
Considerable
phenotypic
variation
under
identical
culture
conditions
limits
the
potential
of
stem-cell-based
embryo
models
(SEMs)
in
basic
and
applied
research.
The
biological
processes
causing
this
seemingly
stochastic
remain
unclear.
Here,
we
investigated
roots
by
parallel
recording
transcriptomic
states
morphological
history
individual
structures
modeling
embryonic
trunk
formation.
Machine
learning
integration
time-resolved
single-cell
RNA
sequencing
with
imaging-based
profiling
identified
early
features
predictive
end
states.
Leveraging
power
revealed
that
imbalance
oxidative
phosphorylation
glycolysis
results
aberrant
morphology
a
neural
lineage
bias,
which
confirmed
metabolic
measurements.
Accordingly,
interventions
improved
Collectively,
our
work
establishes
divergent
as
drivers
offers
broadly
applicable
framework
to
chart
predict
organoids
SEMs.
strategy
can
be
used
identify
control
underlying
processes,
ultimately
increasing
reproducibility.
Developmental Cell,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 1, 2024
During
neural
tube
(NT)
development,
the
notochord
induces
an
organizer,
floorplate,
which
secretes
Sonic
Hedgehog
(SHH)
to
pattern
progenitors.
Conversely,
NT
organoids
(NTOs)
from
embryonic
stem
cells
(ESCs)
spontaneously
form
floorplates
without
notochord,
demonstrating
that
can
self-organize
inducers.
Here,
we
investigated
floorplate
self-organization
in
clonal
mouse
NTOs.
Expression
of
marker
FOXA2
was
initially
spatially
scattered
before
resolving
into
multiple
clusters,
underwent
competition
and
sorting,
resulting
a
stable
"winning"
floorplate.
We
identified
BMP
signaling
governed
long-range
cluster
competition.
FOXA2+
clusters
expressed
BMP4,
suppressing
receiving
while
simultaneously
expressing
BMP-inhibitor
NOGGIN,
promoting
persistence.
Noggin
mutation
perturbed
formation
NTOs
vivo
at
mid/hindbrain
regions,
how
autonomously
notochord.
Identifying
pathways
governing
organizer
is
critical
for
harnessing
developmental
plasticity
tissue
engineering.
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.