Communications Biology,
Год журнала:
2022,
Номер
5(1)
Опубликована: Апрель 29, 2022
Abstract
Heart
organoids
have
the
potential
to
generate
primary
heart-like
anatomical
structures
and
hold
great
promise
as
in
vitro
models
for
cardiac
disease.
However,
their
properties
not
yet
been
fully
studied,
which
hinders
wide
spread
application.
Here
we
report
development
of
differentiation
systems
ventricular
atrial
heart
organoids,
enabling
study
diseases
with
chamber
defects.
We
show
that
our
chamber-specific
comprising
major
cell
types,
use
single
RNA
sequencing
together
sample
multiplexing
characterize
cells
generate.
To
end,
developed
a
machine
learning
label
transfer
approach
leveraging
type,
chamber,
laterality
annotations
available
human
fetal
cells.
then
used
this
model
analyze
organoid
from
an
isogeneic
line
carrying
Ebstein’s
anomaly
associated
genetic
variant
NKX2-5
,
successfully
recapitulated
disease’s
atrialized
In
summary,
established
workflow
integrating
computational
analysis
normal
disease
states.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Авг. 26, 2021
Abstract
Congenital
heart
defects
constitute
the
most
common
human
birth
defect,
however
understanding
of
how
these
disorders
originate
is
limited
by
our
ability
to
model
accurately
in
vitro.
Here
we
report
a
method
generate
developmentally
relevant
organoids
self-assembly
using
pluripotent
stem
cells.
Our
procedure
fully
defined,
efficient,
reproducible,
and
compatible
with
high-content
approaches.
Organoids
are
generated
through
three-step
Wnt
signaling
modulation
strategy
chemical
inhibitors
growth
factors.
Heart
comparable
age-matched
fetal
cardiac
tissues
at
transcriptomic,
structural,
cellular
level.
They
develop
sophisticated
internal
chambers
well-organized
multi-lineage
cell
types,
recapitulate
field
formation
atrioventricular
specification,
complex
vasculature,
exhibit
robust
functional
activity.
We
also
show
that
organoid
platform
can
recreate
metabolic
associated
congenital
defects,
as
demonstrated
an
vitro
pregestational
diabetes-induced
defects.
Cell,
Год журнала:
2022,
Номер
185(15), С. 2756 - 2769
Опубликована: Июль 1, 2022
For
decades,
insight
into
fundamental
principles
of
human
biology
and
disease
has
been
obtained
primarily
by
experiments
in
animal
models.
While
this
allowed
researchers
to
understand
many
biological
processes
great
detail,
some
developmental
mechanisms
have
proven
difficult
study
due
inherent
species
differences.
The
advent
organoid
technology
more
than
10
years
ago
established
laboratory-grown
organ
tissues
as
an
additional
model
system
recapitulate
human-specific
aspects
biology.
use
3D
organoids,
well
other
advances
single-cell
technologies,
revealed
unprecedented
insights
mechanisms,
especially
those
that
distinguish
humans
from
species.
This
review
highlights
novel
with
a
focus
on
how
generated
better
understanding
development
disease.
Cell stem cell,
Год журнала:
2022,
Номер
29(10), С. 1445 - 1458.e8
Опубликована: Сен. 8, 2022
Several
in
vitro
models
have
been
developed
to
recapitulate
mouse
embryogenesis
solely
from
embryonic
stem
cells
(ESCs).
Despite
mimicking
many
aspects
of
early
development,
they
fail
capture
the
interactions
between
and
extraembryonic
tissues.
To
overcome
this
difficulty,
we
a
ESC-based
model
that
reconstitutes
pluripotent
ESC
lineage
two
lineages
post-implantation
embryo
by
transcription-factor-mediated
induction.
This
unified
recapitulates
developmental
events
day
5.5
8.5,
including
gastrulation;
formation
anterior-posterior
axis,
brain,
beating
heart
structure;
development
tissues,
yolk
sac
chorion.
Comparing
single-cell
RNA
sequencing
individual
structures
with
time-matched
natural
embryos
identified
remarkably
similar
transcriptional
programs
across
but
also
showed
when
where
diverges
program.
Our
findings
demonstrate
an
extraordinary
plasticity
ESCs
self-organize
generate
whole-embryo-like
structure.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Авг. 18, 2022
Organoids
provide
an
accessible
in
vitro
system
to
mimic
the
dynamics
of
tissue
regeneration
and
development.
However,
long-term
live-imaging
organoids
remains
challenging.
Here
we
present
experimental
image-processing
framework
capable
turning
light-sheet
imaging
intestinal
into
digital
organoids.
The
combines
specific
optimization
combined
with
data
processing
via
deep
learning
techniques
segment
single
organoids,
their
lumen,
cells
nuclei
3D
over
long
periods
time.
By
linking
lineage
trees
corresponding
segmentation
meshes
for
each
organoid,
extracted
information
is
visualized
using
a
web-based
"Digital
Organoid
Viewer"
tool
allowing
understanding
multivariate
multiscale
data.
We
also
show
backtracking
interest,
providing
detailed
about
history
within
entire
organoid
contexts.
Furthermore,
cytokinesis
failure
regenerative
that
these
never
reside
crypt,
hinting
at
scale
control
on
cellular
fidelity.
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.
