International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(14), С. 7750 - 7750
Опубликована: Июль 15, 2024
Since
the
emergence
of
first
cerebral
organoid
(CO)
in
2013,
advancements
have
transformed
central
nervous
system
(CNS)
research.
Initial
efforts
focused
on
studying
morphogenesis
COs
and
creating
reproducible
models.
Numerous
methodologies
been
proposed,
enabling
design
brain
to
represent
specific
regions
spinal
cord
structures.
CNS
organoids
now
facilitate
study
a
wide
range
diseases,
from
infections
tumors,
which
were
previously
difficult
investigate.
We
summarize
major
organoids,
concerning
morphogenetic
designs
disease
examine
development
fabrication
procedures
how
these
enabled
generation
region-specific
highlight
application
various
demonstrating
versatility
potential
models
advancing
our
understanding
complex
conditions.
discuss
current
challenges
field,
including
issues
related
reproducibility,
scalability,
accurate
recapitulation
vivo
environment.
provide
an
outlook
prospective
studies
future
directions.
This
review
aims
comprehensive
overview
state-of-the-art
research,
highlighting
key
developments,
challenges,
prospects
field.
Nature,
Год журнала:
2024,
Номер
635(8039), С. 690 - 698
Опубликована: Ноя. 20, 2024
Human
neural
organoids,
generated
from
pluripotent
stem
cells
in
vitro,
are
useful
tools
to
study
human
brain
development,
evolution
and
disease.
However,
it
is
unclear
which
parts
of
the
covered
by
existing
protocols,
has
been
difficult
quantitatively
assess
organoid
variation
fidelity.
Here
we
integrate
36
single-cell
transcriptomic
datasets
spanning
26
protocols
into
one
integrated
cell
atlas
totalling
more
than
1.7
million
cells1–26.
Mapping
developing
references27–30
shows
primary
types
states
that
have
estimates
similarity
between
counterparts
across
protocols.
We
provide
a
programmatic
interface
browse
query
new
datasets,
showcase
power
annotate
evaluate
Finally,
show
can
be
used
as
diverse
control
cohort
compare
models
disease,
identifying
genes
pathways
may
underlie
pathological
mechanisms
with
models.
The
will
fidelity,
characterize
perturbed
diseased
facilitate
protocol
development.
A
integrating
counterparts,
showing
potential
fidelity
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Март 20, 2024
Stem
cell-derived
organoid
technology
is
a
powerful
tool
that
revolutionizes
the
field
of
biomedical
research
and
extends
scope
our
understanding
human
biology
diseases.
Brain
organoids
especially
open
an
opportunity
for
brain
modeling
many
neurological
diseases,
which
have
lagged
due
to
inaccessibility
samples
lack
similarity
with
other
animal
models.
can
be
generated
through
various
protocols
mimic
whole
or
region-specific.
To
provide
overview
technology,
we
summarize
currently
available
list
several
factors
consider
before
choosing
protocols.
We
also
outline
limitations
current
challenges
need
solved
in
future
investigation
development
pathobiology.
Stem Cell Reports,
Год журнала:
2024,
Номер
19(6), С. 796 - 816
Опубликована: Май 16, 2024
Human
brain
organoid
models
have
emerged
as
a
promising
tool
for
studying
human
development
and
function.
These
preserve
genetics
recapitulate
some
aspects
of
development,
while
facilitating
manipulation
in
an
vitro
setting.
Despite
their
potential
to
transform
biology
medicine,
concerns
persist
about
fidelity.
To
fully
harness
potential,
it
is
imperative
establish
reliable
analytic
methods,
ensuring
rigor
reproducibility.
Here,
we
review
current
analytical
platforms
used
characterize
forebrain
cortical
organoids,
highlight
challenges,
propose
recommendations
future
studies
achieve
greater
precision
uniformity
across
laboratories.
Cells,
Год журнала:
2024,
Номер
13(14), С. 1176 - 1176
Опубликована: Июль 10, 2024
Autism
spectrum
disorders
(ASDs)
are
complex
neurodevelopmental
conditions
characterized
by
deficits
in
social
interaction
and
communication,
as
well
repetitive
behaviors.
Although
the
etiology
of
ASD
is
multifactorial,
with
both
genetic
environmental
factors
contributing
to
its
development,
a
strong
basis
widely
recognized.
Recent
research
has
identified
numerous
mutations
genomic
rearrangements
associated
ASD-characterizing
genes
involved
brain
development.
Alterations
developmental
programs
particularly
harmful
during
critical
periods
Notably,
studies
have
indicated
that
disruptions
occurring
second
trimester
pregnancy
affect
cortical
while
disturbances
perinatal
early
postnatal
period
cerebellar
The
defects
must
be
viewed
context
role
cerebellum
cognitive
processes,
which
now
established.
present
review
emphasizes
complexity
neuropathological
mechanisms
underlying
aims
provide
insights
into
involvement
disorder,
focusing
on
recent
advances
molecular
landscape
governing
development
humans.
Furthermore,
we
highlight
when
neurons
ASD-associated
may
play
cortico–cerebellar
circuits.
Finally,
discuss
improvements
protocols
for
generating
organoids
recapitulate
long
maturation
this
organ.
These
models,
if
generated
from
patient-induced
pluripotent
stem
cells
(iPSC),
could
valuable
approach
elucidate
contribution
defective
pathology
inform
diagnostic
therapeutic
strategies.
Disease Models & Mechanisms,
Год журнала:
2024,
Номер
17(7)
Опубликована: Июль 1, 2024
ABSTRACT
Pontocerebellar
hypoplasia
type
2a
(PCH2a)
is
an
ultra-rare,
autosomal
recessive
pediatric
disorder
with
limited
treatment
options.
Its
anatomical
hallmark
of
the
cerebellum
and
pons
accompanied
by
progressive
microcephaly.
A
homozygous
founder
variant
in
TSEN54,
which
encodes
a
tRNA
splicing
endonuclease
(TSEN)
complex
subunit,
causal.
The
pathological
mechanism
PCH2a
remains
unknown
due
to
lack
model
system.
Therefore,
we
developed
human
models
using
regionalized
neural
organoids.
We
generated
induced
pluripotent
stem
cell
(iPSC)
lines
from
three
males
genetically
confirmed
subsequently
differentiated
cerebellar
neocortical
Mirroring
clinical
neuroimaging
findings,
organoids
were
reduced
size
compared
controls
starting
early
differentiation.
Neocortical
demonstrated
milder
growth
deficits.
Although
did
not
upregulate
apoptosis,
their
zones
showed
altered
proliferation
kinetics,
increased
at
day
30
50
controls.
In
summary,
PCH2a,
providing
foundation
for
deciphering
brain
region-specific
disease
mechanisms.
Our
first
analyses
suggest
neurodevelopmental
aspect
PCH2a.
Frontiers in Cellular Neuroscience,
Год журнала:
2025,
Номер
18
Опубликована: Янв. 6, 2025
Precision,
or
personalized,
medicine
aims
to
stratify
patients
based
on
variable
pathogenic
signatures
optimize
the
effectiveness
of
disease
prevention
and
treatment.
This
approach
is
favorable
in
context
brain
disorders,
which
are
often
heterogeneous
their
pathophysiological
features,
patterns
progression
treatment
response,
resulting
limited
therapeutic
standard-of-care.
Here
we
highlight
transformative
role
that
human
induced
pluripotent
stem
cell
(hiPSC)-derived
neural
models
poised
play
advancing
precision
for
particularly
emerging
innovations
improve
relevance
hiPSC
physiology.
hiPSCs
derived
from
accessible
patient
somatic
cells
can
produce
various
types
tissues;
current
efforts
increase
complexity
these
models,
incorporating
region-specific
tissues
non-neural
microenvironment,
providing
increasingly
relevant
insights
into
human-specific
neurobiology.
Continued
advances
tissue
engineering
combined
with
genomics,
high-throughput
screening
imaging
strengthen
physiological
thus
ability
uncover
mechanisms,
vulnerabilities,
fluid-based
biomarkers
will
have
real
impact
neurological
True
understanding,
however,
necessitates
integration
hiPSC-neural
biophysical
data,
including
quantitative
neuroimaging
representations.
We
discuss
recent
cellular
neuroscience
provide
direct
connections
through
generative
AI
modeling.
Our
focus
great
potential
synergy
between
pave
way
personalized
becoming
a
viable
option
suffering
neuropathologies,
rare
epileptic
neurodegenerative
disorders.
