bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Сен. 3, 2022
Abstract
Single-cell
level
characterization
of
embryonic
development
is
a
major
benchmark
human
developmental
biology.
Spatiotemporal
analysis
stem-cell-derived
embryos
offers
conceptual
and
technical
advances
in
the
field.
Here,
we
defined
single-cell
spatiotemporal
gene
expression
landscape
with
organoids.
We
established
organoid
(HEMO)
from
expanded
potential
stem
cells
achieved
both
extraembryonic
tissues
same
organoid.
Time-series
RNA
sequencing
paired
resolution
spatial
revealed
signatures
such
as
placenta,
yolk
sac
hematopoiesis
neural
crest,
blood
vessels,
cardiac
mesoderm.
Hematopoietic
eventually
predominated
HEMO
erythropoiesis,
mekagaryopiesis,
myelopoiesis.
Cell-cell
communication
network
demonstrated
that
trophoblast-like
supplied
WNT
signaling
crest
to
facilitate
maturation
migration.
transcriptomics
erythro-megakaryopoietic
niche.
Vitronectin-integrin
signaling,
contributor
megakaryocyte
maturation,
was
predominant
niche
fetal
samples.
Overall,
our
study
Highlights
Modeling
Used
10X
Chromium
Visium
define
regulator
EMT
VTN-ITGA2B
main
Mk
within
Graphical
abstract
Trends in Cell Biology,
Год журнала:
2021,
Номер
31(9), С. 747 - 759
Опубликована: Июль 22, 2021
3D
gastruloids,
aggregates
of
embryonic
stem
cells
that
recapitulate
key
aspects
gastrula-stage
embryos,
have
emerged
as
a
powerful
tool
to
study
the
early
stages
mammalian
post-implantation
development
in
vitro.
Owing
their
tractable
nature
and
relative
ease
by
which
they
can
be
generated
large
numbers,
gastruloids
provide
an
unparalleled
opportunity
normal
pathological
embryogenesis
from
bottom-up
perspective
high-throughput
manner.
Here,
we
review
how
gastruloid
models
exploited
deepen
our
understanding
development.
In
addition,
discuss
current
limitations,
potential
clinical
applications,
ethical
implications
this
emerging
model
system.
ABSTRACT
During
embryogenesis,
organisms
acquire
their
shape
given
boundary
conditions
that
impose
geometrical,
mechanical
and
biochemical
constraints.
A
detailed
integrative
understanding
how
these
morphogenetic
information
modules
pattern
the
mammalian
embryo
is
still
lacking,
mostly
owing
to
inaccessibility
of
in
vivo
for
direct
observation
manipulation.
These
impediments
are
circumvented
by
developmental
engineering
embryo-like
structures
(stembryos)
from
pluripotent
stem
cells
easy
access,
track,
manipulate
scale.
Here,
we
explain
unlocking
distinct
levels
architecture
through
controlled
modulations
cellular
environment
enables
identification
minimal
sets
inputs
necessary
embryo.
We
detail
this
can
be
complemented
with
precise
measurements
manipulations
tissue
biochemistry,
mechanics
geometry
across
spatial
temporal
scales
provide
insights
into
mechanochemical
feedback
loops
governing
morphogenesis.
Finally,
discuss
how,
even
absence
active
manipulations,
stembryos
display
intrinsic
phenotypic
variability
leveraged
define
constraints
ensure
reproducible
morphogenesis
vivo.
During
gastrulation,
early
embryos
specify
and
reorganise
the
topology
of
their
germ
layers.
Surprisingly,
this
fundamental
process
does
not
appear
to
be
rigidly
constrained
by
evolutionary
pressures;
instead,
morphology
gastrulation
is
highly
variable
throughout
animal
kingdom.
Recent
experimental
results
demonstrate
that
it
possible
generate
different
alternative
modes
in
single
organisms,
such
as
cnidarian,
arthropod
vertebrate
embryos.
Here,
we
review
mechanisms
underlie
plasticity
both
when
experimentally
manipulated
during
evolution.
Using
insights
obtained
from
these
experiments
discuss
effects
increase
yolk
volume
on
provide
new
into
two
crucial
innovations
amniote
gastrulation:
transition
a
ring-shaped
mesoderm
domain
anamniotes
crescent-shaped
amniotes,
evolution
reptilian
blastoporal
plate/canal
avian
primitive
streak.
Minimal
in
vitro
systems
composed
of
embryonic
stem
cells
(ESCs)
have
been
shown
to
recapitulate
the
establishment
anteroposterior
(AP)
axis.
In
contrast
native
embryo,
ESC
aggregates
-
such
as
gastruloids
can
break
symmetry,
which
is
demarcated
by
polarization
mesodermal
marker
T,
autonomously
without
any
localized
external
cues.
However,
associated
earliest
patterning
events,
spatial
restriction
cell
fates
and
concomitant
transcriptional
changes,
remain
poorly
understood.
Here,
we
dissect
dynamics
AP
axis
mouse
gastruloids,
particularly
before
Wnt
stimulation.
Through
single-cell
RNA
sequencing,
identify
key
state
transitions
molecular
signatures
T+
T-
populations
underpinning
polarization.
We
also
show
that
this
process
robust
modifications
aggregate
size.
Finally,
transcriptomic
comparison
with
embryo
indicates
develop
similar
mesendodermal
types,
despite
initial
differences
their
primed
pluripotent
populations,
adopt
a
more
mesenchymal
lieu
an
epiblast-like
transcriptome.
Hence,
our
findings
suggest
possibility
alternate
states
vivo
converge
onto
fates.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 8, 2024
Abstract
Brown
algae
are
multicellular
photosynthetic
organisms
that
have
evolved
independently
of
plants
and
other
algae.
Apart
from
studies
on
the
polarisation
Fucus
zygote
in
1990s,
little
is
known
about
mechanisms
controlling
embryogenesis
these
organisms.
Here,
we
studied
determinism
kelp
Saccharina
latissima,
focusing
formation
its
body
axes.
This
alga
initially
develops
an
oblong
embryo
formed
a
cell
monolayer,
which
subsequently
thickens;
growth
axes
then
established
temporally
distinct
stages,
starting
with
dominant
apico-basal
axis.
Our
experiments
focused
role
stalk,
empty
retains
attached
to
maternal
tissue,
development
mature
embryos.
In
response
removal
embryos
developed
as
monolayered
disc
rather
than
elongated
blade,
demonstrating
attachment
stalk
inhibits
medio-lateral
axis
at
onset
embryogenesis.
addition,
compared
cells
detached
were
smaller
displayed
altered
shape.
The
topology
tissue
was
also
disrupted,
had
higher
number
neighbours.
Observation
division
patterns
just
after
showed
represses
longitudinal
divisions,
thereby
reinforcing
establishment
main
unique
quantitative
study
brown
algal
revealed
that,
kelps,
signal
(MUM
for
unknown
message)
necessary
organisation
growing
embryonic
tissues.
discovered
although
persists
several
weeks
until
reaches
least
500
cells,
MUM
emitted
first
4
days
fertilisation
only,
before
8-cell
stage.
Finally,
transplantation
indicated
does
not
diffuse
seawater,
but
requires
contact
between
stalk.
potential
chemical
or
mechanical
nature
discussed.
Organoids
and
stem-cell-based
embryo
models
(SEMs)
are
imperfect
organ
or
representations
that
explore
a
much
larger
space
of
possible
forms,
morphospace,
compared
to
their