International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(15), P. 12528 - 12528
Published: Aug. 7, 2023
Brain
organoids
are
three-dimensional
(3D)
structures
derived
from
human
pluripotent
stem
cells
(hPSCs)
that
reflect
early
brain
organization.
These
contain
different
cell
types,
including
neurons
and
glia,
similar
to
those
found
in
the
brain.
Human
provide
unique
opportunities
model
features
of
development
not
well-reflected
animal
models.
Compared
with
traditional
cultures
models,
offer
a
more
accurate
representation
function,
rendering
them
suitable
models
for
neurodevelopmental
diseases.
In
particular,
patients’
have
enabled
researchers
study
diseases
at
stages
gain
better
understanding
disease
mechanisms.
Multi-brain
regional
assembloids
allow
investigation
interactions
between
distinct
regions
while
achieving
higher
level
consistency
molecular
functional
characterization.
Although
possess
promising
features,
their
usefulness
is
limited
by
several
unresolved
constraints,
cellular
stress,
hypoxia,
necrosis,
lack
high-fidelity
maturation,
circuit
formation.
this
review,
we
discuss
studies
overcome
natural
limitations
organoids,
emphasizing
importance
combinations
all
neural
such
as
glia
(astrocyte,
oligodendrocytes,
microglia)
vascular
cells.
Additionally,
considering
similarity
developing
brain,
regionally
patterned
organoid-derived
(NSCs)
could
serve
scalable
source
replacement
therapy.
We
highlight
potential
application
therapy
within
field.
Nature,
Journal Year:
2023,
Volume and Issue:
621(7978), P. 373 - 380
Published: Sept. 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.
Stem Cell Reports,
Journal Year:
2023,
Volume and Issue:
18(6), P. 1255 - 1270
Published: June 1, 2023
In
the
past
decade,
term
organoid
has
moved
from
obscurity
to
common
use
describe
a
3D
in
vitro
cellular
model
of
tissue
that
recapitulates
structural
and
functional
elements
vivo
organ
it
models.
The
is
now
applied
structures
formed
as
result
two
distinct
processes:
capacity
for
adult
epithelial
stem
cells
re-create
niche
ability
direct
differentiation
pluripotent
self-organizing
multicellular
organogenesis.
While
these
fields
rely
upon
different
cell
types
recapitulate
processes,
both
share
challenges
around
robustness,
accuracy,
reproducibility.
Critically,
organoids
are
not
organs.
This
commentary
serves
discuss
challenges,
how
they
impact
genuine
utility,
shine
light
on
need
improve
standards
all
approaches.
