Frontiers in Cell and Developmental Biology,
Год журнала:
2021,
Номер
9
Опубликована: Июль 2, 2021
Astrocytes
are
the
key
component
of
central
nervous
system
(CNS),
serving
as
pivotal
regulators
neuronal
synapse
formation
and
maturation
through
their
ability
to
dynamically
bidirectionally
communicate
with
synapses
throughout
life.
In
past
20
years,
numerous
astrocyte-derived
molecules
promoting
synaptogenesis
have
been
discovered.
However,
our
understanding
cell
biological
basis
underlying
intra-neuron
processes
astrocyte-mediated
is
still
in
its
infancy.
Here,
we
provide
a
comprehensive
overview
various
ways
astrocytes
talk
neurons,
highlight
astrocytes’
heterogeneity
that
allow
them
displays
regional-specific
capabilities
boosting
synaptogenesis.
Finally,
conclude
promises
future
directions
on
how
organoids
generated
from
human
induced
pluripotent
stem
cells
(hiPSCs)
effectively
address
signaling
pathways
employ
synaptic
development.
Annual Review of Neuroscience,
Год журнала:
2022,
Номер
45(1), С. 23 - 39
Опубликована: Янв. 5, 2022
Organoids
are
3D
cell
culture
systems
derived
from
human
pluripotent
stem
cells
that
contain
tissue
resident
types
and
reflect
features
of
early
organization.
Neural
organoids
a
particularly
innovative
scientific
advance
given
the
lack
accessibility
developing
brain
intractability
neurological
diseases.
have
become
an
invaluable
approach
to
model
development
not
well
reflected
in
animal
models.
also
hold
promise
for
study
atypical
cellular,
molecular,
genetic
underscore
Additionally,
may
provide
platform
testing
therapeutics
potential
source
replacement
approaches
injury
or
disease.
Despite
promising
organoids,
their
broad
utility
is
tempered
by
variety
limitations
yet
be
overcome,
including
high-fidelity
types,
limited
maturation,
physiology,
arealization,
limit
reliability
certain
applications.
Nature,
Год журнала:
2023,
Номер
621(7978), С. 373 - 380
Опубликована: Сен. 13, 2023
Abstract
The
development
of
the
human
brain
involves
unique
processes
(not
observed
in
many
other
species)
that
can
contribute
to
neurodevelopmental
disorders
1–4
.
Cerebral
organoids
enable
study
a
context.
We
have
developed
CRISPR–human
organoids–single-cell
RNA
sequencing
(CHOOSE)
system,
which
uses
verified
pairs
guide
RNAs,
inducible
CRISPR–Cas9-based
genetic
disruption
and
single-cell
transcriptomics
for
pooled
loss-of-function
screening
mosaic
organoids.
Here
we
show
perturbation
36
high-risk
autism
spectrum
disorder
genes
related
transcriptional
regulation
uncovers
their
effects
on
cell
fate
determination.
find
dorsal
intermediate
progenitors,
ventral
progenitors
upper-layer
excitatory
neurons
are
among
most
vulnerable
types.
construct
developmental
gene
regulatory
network
cerebral
from
transcriptomes
chromatin
modalities
identify
disorder-associated
perturbation-enriched
modules.
Perturbing
members
BRG1/BRM-associated
factor
(BAF)
remodelling
complex
leads
enrichment
telencephalon
progenitors.
Specifically,
mutating
BAF
subunit
ARID1B
affects
transition
oligodendrocyte
interneuron
precursor
cells,
phenotype
confirmed
patient-specific
induced
pluripotent
stem
cell-derived
Our
paves
way
high-throughput
phenotypic
characterization
disease
susceptibility
organoid
models
with
state,
molecular
pathway
readouts.
Organoids
are
three-dimensional
(3D)
miniaturized
versions
of
organs
or
tissues
that
derived
from
cells
with
stem
potential
and
can
self-organize
differentiate
into
3D
cell
masses,
recapitulating
the
morphology
functions
their
in
vivo
counterparts.
Organoid
culture
is
an
emerging
technology,
organoids
various
tissues,
such
as
brain,
lung,
heart,
liver,
kidney,
have
been
generated.
Compared
traditional
bidimensional
culture,
organoid
systems
unique
advantage
conserving
parental
gene
expression
mutation
characteristics,
well
long-term
maintenance
function
biological
characteristics
vitro.
All
these
features
open
up
new
opportunities
for
drug
discovery,
large-scale
screening,
precision
medicine.
Another
major
application
disease
modeling,
especially
hereditary
diseases
difficult
to
model
vitro
modeled
by
combining
genome
editing
technologies.
Herein,
we
introduce
development
current
advances
technology
field.
We
focus
on
applications
basic
biology
clinical
research,
also
highlight
limitations
future
perspectives.
hope
this
review
provide
a
valuable
reference
developments
organoids.
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.
Nature,
Год журнала:
2023,
Номер
622(7982), С. 359 - 366
Опубликована: Сен. 27, 2023
Abstract
The
assembly
of
cortical
circuits
involves
the
generation
and
migration
interneurons
from
ventral
to
dorsal
forebrain
1–3
,
which
has
been
challenging
study
at
inaccessible
stages
late
gestation
early
postnatal
human
development
4
.
Autism
spectrum
disorder
other
neurodevelopmental
disorders
(NDDs)
have
associated
with
abnormal
interneuron
5
but
these
NDD
genes
affect
migration,
how
they
mediate
effects
remains
unknown.
We
previously
developed
a
platform
in
subpallial
organoids
assembloids
6
Here
we
integrate
CRISPR
screening
investigate
involvement
425
development.
first
screen
aimed
revealed
13
candidate
genes,
including
CSDE1
SMAD4
subsequently
conducted
an
more
than
1,000
that
identified
33
cytoskeleton-related
endoplasmic
reticulum-related
gene
LNPK
discovered
that,
during
reticulum
is
displaced
along
leading
neuronal
branch
before
nuclear
translocation.
deletion
interfered
this
displacement
resulted
migration.
These
results
highlight
power
CRISPR-assembloid
systematically
map
onto
reveal
disease
mechanisms.
