Stem Cell Reports,
Год журнала:
2021,
Номер
16(5), С. 1117 - 1141
Опубликована: Май 1, 2021
Detailed
studies
of
the
embryo
allow
an
increasingly
mechanistic
understanding
development,
which
has
proved
profound
relevance
to
human
disease.
The
last
decade
seen
in
vitro
cultured
stem
cell-based
models
development
flourish,
provide
alternative
for
accessible
experimentation.
However,
usefulness
any
model
will
be
determined
by
how
accurately
it
reflects
vivo
embryonic
and/or
extent
facilitates
new
discoveries.
Stringent
benchmarking
is
thus
important
consideration
this
growing
field.
Here
we
overview
means
evaluate
both
properties
cells,
building
blocks
most
models,
as
well
current
and
future
models.
ABSTRACT
As
the
crucial
non-cellular
component
of
tissues,
extracellular
matrix
(ECM)
provides
both
physical
support
and
signaling
regulation
to
cells.
Some
ECM
molecules
provide
a
fibrillar
environment
around
cells,
while
others
sheet-like
basement
membrane
scaffold
beneath
epithelial
In
this
Review,
we
focus
on
recent
studies
investigating
mechanical,
biophysical
cues
provided
developing
tissues
by
different
types
in
variety
organisms.
addition,
discuss
how
helps
regulate
tissue
morphology
during
embryonic
development
governing
key
elements
cell
shape,
adhesion,
migration
differentiation.
Post-implantation
embryogenesis
is
a
highly
dynamic
process
comprising
multiple
lineage
decisions
and
morphogenetic
changes
that
are
inaccessible
to
deep
analysis
in
vivo.
We
found
pluripotent
mouse
embryonic
stem
cells
(mESCs)
form
aggregates
upon
embedding
an
extracellular
matrix
compound
induce
the
formation
of
organized
"trunk-like
structures"
(TLSs)
neural
tube
somites.
Comparative
single-cell
RNA
sequencing
confirmed
this
analogous
development
follows
same
stepwise
gene-regulatory
program.
Tbx6
knockout
TLSs
developed
additional
tubes
mirroring
mutant
phenotype,
chemical
modulation
could
excess
somite
formation.
thus
reveal
advanced
level
self-organization
provide
powerful
platform
for
investigating
post-implantation
dish.
Gene
regulatory
networks
and
tissue
morphogenetic
events
drive
the
emergence
of
shape
function:
pillars
embryo
development.
Although
model
systems
offer
a
window
into
molecular
biology
cell
fate
shape,
mechanistic
studies
our
own
development
have
so
far
been
technically
ethically
challenging.
However,
recent
technical
developments
provide
tools
to
describe,
manipulate
mimic
human
embryos
in
dish,
thus
opening
new
avenue
exploring
Here,
I
discuss
evidence
that
supports
role
for
crosstalk
between
during
early
embryogenesis.
This
is
critical
developmental
period,
when
body
plan
laid
out
many
pregnancies
fail.
Dissecting
basic
mechanisms
coordinate
will
generate
an
integrated
understanding
embryogenesis
strategies
therapeutic
intervention
pregnancy
loss.
Advanced Materials,
Год журнала:
2021,
Номер
33(43)
Опубликована: Сен. 9, 2021
Abstract
Organoids
are
lumen‐containing
multicellular
structures
that
recapitulate
key
features
of
the
organs,
and
increasingly
used
in
models
disease,
drug
testing,
regenerative
medicine.
Recent
work
has
3D
culture
to
form
organoids
from
human
induced
pluripotent
stem
cells
(hiPSCs)
reconstituted
basement
membrane
(rBM)
matrices.
However,
rBM
matrices
offer
little
control
over
microenvironment.
More
generally,
role
matrix
viscoelasticity
directing
lumen
formation
remains
unknown.
Here,
viscoelastic
alginate
hydrogels
with
independently
tunable
stress
relaxation
(viscoelasticity),
stiffness,
arginine–glycine–aspartate
(RGD)
ligand
density
study
hiPSC
morphogenesis
culture.
A
phase
diagram
shows
how
these
properties
is
reported.
Higher
RGD
fast
promote
viability,
proliferation,
apicobasal
polarization,
formation,
while
slow
at
low
densities
triggers
apoptosis.
Notably,
hiPSCs
maintain
pluripotency
for
much
longer
times
than
reported
Lumen
regulated
by
actomyosin
contractility
accompanied
translocation
Yes‐associated
protein
(YAP)
nucleus
cytoplasm.
The
results
reveal
as
a
potent
factor
regulating
cell
provide
new
insights
into
engineered
biomaterials
may
be
leveraged
build
organoids.
During
mammalian
gastrulation,
germ
layers
arise
and
are
shaped
into
the
body
plan
while
extraembryonic
sustain
embryo.
Human
embryonic
stem
cells,
cultured
with
BMP4
on
extracellular
matrix
micro-discs,
reproducibly
differentiate
gastruloids,
expressing
markers
of
cells
in
radial
arrangement.
Using
single-cell
RNA
sequencing
cross-species
comparisons
mouse,
cynomolgus
monkey
gastrulae,
post-implantation
human
embryos,
we
reveal
that
gastruloids
contain
transcriptionally
similar
to
epiblast,
ectoderm,
mesoderm,
endoderm,
primordial
trophectoderm,
amnion.
Upon
gastruloid
dissociation,
single
reseeded
onto
micro-discs
were
motile
aggregated
same
but
segregated
from
distinct
cell
types.
Ectodermal
endodermal
mixed
mesodermal
cells.
Our
work
demonstrates
system
models
primate-specific
features
embryogenesis,
exhibit
evolutionarily
conserved
sorting
behaviors.
This
generates
a
resource
for
transcriptomes
differentiated
stereotyped
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Июнь 2, 2021
Abstract
Generating
properly
differentiated
embryonic
structures
in
vitro
from
pluripotent
stem
cells
remains
a
challenge.
Here
we
show
that
instruction
of
aggregates
mouse
with
an
experimentally
engineered
morphogen
signalling
centre,
functions
as
organizer,
results
the
development
embryo-like
entities
(embryoids).
In
situ
hybridization,
immunolabelling,
cell
tracking
and
transcriptomic
analyses
these
embryoids
form
three
germ
layers
through
gastrulation
process
they
exhibit
wide
range
developmental
structures,
highly
similar
to
neurula-stage
embryos.
Embryoids
are
organized
around
axial
chordamesoderm,
dorsal
neural
plate
displays
histological
properties
murine
embryo
neuroepithelium
folds
into
tube
patterned
antero-posteriorly
posterior
midbrain
tip
tail.
Lateral
display
somitic
intermediate
mesoderm,
beating
cardiac
tissue
anteriorly
formation
vasculature
network.
Ventrally,
differentiate
primitive
gut
tube,
which
is
both
dorso-ventrally.
Altogether,
provide
model
mammalian
extensive
layer
derivatives
promises
be
powerful
tool
for
studies
disease
modelling.
