Biomedicines,
Год журнала:
2024,
Номер
12(12), С. 2714 - 2714
Опубликована: Ноя. 27, 2024
Cardiovascular
disease
comprises
a
group
of
disorders
affecting
or
originating
within
tissues
and
organs
the
cardiovascular
system;
most,
if
not
all,
will
eventually
result
in
cardiomyocyte
dysfunction
death,
negatively
impacting
cardiac
function.
Effective
models
are
thus
important
for
understanding
crucial
aspects
progression,
while
recent
advancements
stem
cell
biology
have
allowed
use
populations
to
derive
such
models.
These
include
three-dimensional
(3D)
as
cell-based
embryos
(SCME)
well
organoids,
many
which
frequently
derived
from
embryoid
bodies
(EB).
Not
only
can
they
recapitulate
3D
form
function,
but
developmental
programs
governing
self-organization
into
more
complex
well.
Many
different
organoids
SCME
constructs
been
generated
years
recreate
tissue
that
give
rise
its
cellular
composition
unique
morphology.
It
is
purpose
this
narrative
literature
review
describe
summarize
recently
organoid
their
recapitulation
genetic
acquired
disease.
Owing
examined,
focus
on
injury
associated
with
embryonic/fetal
tissues.
Cell stem cell,
Год журнала:
2023,
Номер
30(6), С. 867 - 884.e11
Опубликована: Май 19, 2023
Gastruloids
are
3D
structures
generated
from
pluripotent
stem
cells
recapitulating
fundamental
principles
of
embryonic
pattern
formation.
Using
single-cell
genomic
analysis,
we
provide
a
resource
mapping
cell
states
and
types
during
gastruloid
development
compare
them
with
the
in
vivo
embryo.
We
developed
high-throughput
handling
imaging
pipeline
to
spatially
monitor
symmetry
breaking
report
an
early
spatial
variability
pluripotency
determining
binary
response
Wnt
activation.
Although
gastruloid-core
revert
pluripotency,
peripheral
become
primitive
streak-like.
These
two
populations
subsequently
break
radial
initiate
axial
elongation.
By
performing
compound
screen,
perturbing
thousands
gastruloids,
derive
phenotypic
landscape
infer
networks
genetic
interactions.
Finally,
using
dual
modulation,
improve
formation
anterior
existing
model.
This
work
provides
understand
how
gastruloids
develop
generate
complex
patterns
vitro.
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.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 5, 2023
Abstract
When
cultured
in
three
dimensional
spheroids,
mammalian
stem
cells
can
reproducibly
self-organize
a
single
anterior-posterior
axis
and
sequentially
differentiate
into
structures
resembling
the
primitive
streak
tailbud.
Whereas
embryo’s
body
axes
are
instructed
by
spatially
patterned
extra-embryonic
cues,
it
is
unknown
how
these
cell
gastruloids
break
symmetry
to
define
(A-P)
axis.
Here,
we
use
synthetic
gene
circuits
trace
early
intracellular
signals
predict
cells’
future
position
gastruloid.
We
show
that
Wnt
signaling
evolves
from
homogeneous
state
polarized
state,
identify
critical
6-hour
time
period
when
single-cell
activity
predicts
cellular
position,
prior
appearance
of
patterns
or
morphology.
Single-cell
RNA
sequencing
live-imaging
reveal
Wnt-high
Wnt-low
contribute
distinct
types
suggest
axial
breaking
driven
sorting
rearrangements
involving
differential
adhesion.
further
extend
our
approach
other
canonical
embryonic
pathways,
revealing
even
earlier
heterogeneity
TGFβ
A-P
modulates
during
period.
Our
study
reveals
sequence
dynamic
processes
transform
uniform
aggregate
structure
demonstrates
morphological
emerge
out
movements
absence
exogenous
patterning
cues.
Highlights
Symmetry-breaking
gastruloid
protocol
where
high
posterior
domain.
Synthetic
record
Wnt,
Nodal
BMP
with
resolution.
Heterogeneity
at
96
h
positions
types.
differences
influenced
Nodal/BMP
activity.
FASEB BioAdvances,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 2, 2025
ABSTRACT
Stem
cell‐based
models
of
embryogenesis
have
exploded
in
popularity,
resulting
protocols
with
overlapping
use
some
reagents
and
differential
others.
As
such,
the
precise
contributions
individual
signaling
molecules,
such
as
Chiron
BMP4,
applied
to
whole
or
part
aggregates,
matrices,
Matrigel,
development
these
are
unknown.
Furthermore,
different
methods,
matrices
has
yet
be
directly
compared
under
same
conditions.
In
this
paper,
we
used
a
mouse
embryonic
stem
cell
aggregate
model
compare
BMP4
pulses
(applied
aggregate)
centers
embedded
them
low‐percentage
Matrigel.
Each
factor
had
effects
on
morphology,
Brachyury
protein
expression,
lineage
commitment,
having
pulses.
pulse
was
shown
drive
neural
differentiation,
while
resulted
better
recapitulation
aspects
anterior–posterior
axis
formation,
polarization
expression
anterior
posterior
genes
observed.
This
further
elucidates
inform
decisions
around
experimental
conditions
for
vitro
development.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 4, 2023
Abstract
Establishment
of
the
vertebrate
body
plan
requires
a
combination
extra-embryonic
signalling
to
establish
morphogen
gradients,
and
an
underlying
self-assembly
mechanism
that
contributes
pattern
regulation
robustness.
Gastruloids
are
aggregates
mouse
embryonic
stem
cells
break
morphological
symmetry
polarise
Brachyury
(
Bra
)
expression
in
absence
signals.
However,
by
which
breaking
occurs
is
not
yet
known.
During
gastrulation
axis
elongation,
retinoic
acid
(RA)
Cyp26a1
polarised
along
anteroposterior
axis,
this
critical
for
balancing
decision
self-renew
or
differentiate.
We
found
symmetry-breaking
gastruloids
coincident
with
separation
Aldh1a2
expression,
feedback
from
maintaining
gene
gastruloid
posterior
region.
Furthermore,
we
reveal
short
temporal
window
where
RA
can
negatively
influence
both
expression.
These
observations
lead
us
suggest
how
initial
patterning,
subsequent
evolving
network
topologies
create
defined
boundaries
permits
proper
axial
patterning
growth.
Current Opinion in Genetics & Development,
Год журнала:
2023,
Номер
82, С. 102102 - 102102
Опубликована: Авг. 19, 2023
During
early
development,
extrinsic
cues
prompt
a
collection
of
pluripotent
cells
to
begin
the
extensive
process
cellular
differentiation
that
gives
rise
all
tissues
in
mammalian
embryo,
known
as
gastrulation.
Advances
stem
cell
biology
have
resulted
generation
cell-based
vitro
models
gastrulation
called
gastruloids.
Gastruloids
and
subsequent
gastruloid-based
are
tractable,
scalable
more
accessible
than
embryos.
As
such,
they
opened
an
unprecedented
avenue
for
modelling
self-organisation,
patterning
fate
specification.
This
review
focuses
on
discussing
recent
advances
this
rapidly
moving
research
area,
clarifying
what
structures
model
underlying
signal
hierarchy.
We
highlight
exciting
potential
these
where
field
might
be
heading.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Mammalian
embryonic
size
is
tightly
controlled
with
checkpoints
and
compensatory
mechanisms
correcting
defects.
Here,
we
take
advantage
of
gastruloids,
a
stem
cell
embryoid
system
not
subject
to
most
controls,
study
the
role
in
emergent
properties
mammalian
embryogenesis.
We
report
that
gastruloids
exhibit
robust
morphology
transcriptional
profiles
within
range.
However,
affects
dynamics,
and,
outside
range
morphogenesis,
precision
anterior-posterior
(AP)
axial
elongation.
Gastruloid
elongation
exhibits
active
cellular
contractility,
requires
planar
polarity
(PCP),
adhesion
cell-cell
contact
remodelling.
Smaller
initiate
earlier,
correlated
an
earlier
Brachyury
polarisation.
expression
increases
tissue
fluidity.
Axis
formation
regulated
by
balance
multifoci
coalescence
timing
initiation
programme.
Sizes
beyond
can
modify
relative
composition.
Very
small
aggregates
have
increased
neural
fate
bias,
accompanied
loss
paraxial
mesoderm
mediated
differences
Nodal
signalling
activity.