Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(3), P. 113883 - 113883
Published: March 1, 2024
Phosphomannomutase
2-congenital
disorder
of
glycosylation
(PMM2-CDG)
is
a
rare
inborn
error
metabolism
caused
by
deficiency
the
PMM2
enzyme,
which
leads
to
impaired
protein
glycosylation.
While
presents
with
primarily
neurological
symptoms,
there
limited
knowledge
about
specific
brain-related
changes
deficiency.
Here,
we
demonstrate
aberrant
neural
activity
in
2D
neuronal
networks
from
PMM2-CDG
individuals.
Utilizing
multi-omics
datasets
3D
human
cortical
organoids
(hCOs)
derived
individuals,
identify
widespread
decreases
glycosylation,
highlighting
as
key
pathological
feature
PMM2-CDG,
well
mitochondrial
structure
and
abnormal
glucose
PMM2-deficient
hCOs,
indicating
disturbances
energy
metabolism.
Correlation
between
enzymatic
hCOs
symptom
severity
suggests
that
level
enzyme
function
directly
influences
manifestations.
These
findings
enhance
our
understanding
perturbations
associated
offering
insights
into
underlying
mechanisms
potential
directions
for
therapeutic
interventions.
Cell,
Journal Year:
2024,
Volume and Issue:
187(3), P. 712 - 732.e38
Published: Jan. 8, 2024
Human
brain
development
involves
an
orchestrated,
massive
neural
progenitor
expansion
while
a
multi-cellular
tissue
architecture
is
established.
Continuously
expanding
organoids
can
be
grown
directly
from
multiple
somatic
tissues,
yet
to
date,
solely
established
pluripotent
stem
cells.
Here,
we
show
that
healthy
human
fetal
in
vitro
self-organizes
into
(FeBOs),
phenocopying
aspects
of
vivo
cellular
heterogeneity
and
complex
organization.
FeBOs
expanded
over
long
time
periods.
FeBO
growth
requires
maintenance
integrity,
which
ensures
production
tissue-like
extracellular
matrix
(ECM)
niche,
ultimately
endowing
expansion.
lines
derived
different
areas
the
central
nervous
system
(CNS),
including
dorsal
ventral
forebrain,
preserve
their
regional
identity
allow
probe
positional
identity.
Using
CRISPR-Cas9,
showcase
generation
syngeneic
mutant
for
study
cancer.
Taken
together,
constitute
complementary
CNS
organoid
platform.
Frontiers in Artificial Intelligence,
Journal Year:
2024,
Volume and Issue:
6
Published: Jan. 5, 2024
Human
brain
organoids,
aka
cerebral
organoids
or
earlier
"mini-brains",
are
3D
cellular
models
that
recapitulate
aspects
of
the
developing
human
brain.
They
show
tremendous
promise
for
advancing
our
understanding
neurodevelopment
and
neurological
disorders.
However,
unprecedented
ability
to
model
development
function
Advanced Healthcare Materials,
Journal Year:
2024,
Volume and Issue:
13(21)
Published: Jan. 22, 2024
Brain
organoids
are
3D
in
vitro
culture
systems
derived
from
human
pluripotent
stem
cells
that
self-organize
to
model
features
of
the
(developing)
brain.
This
review
examines
techniques
behind
organoid
generation,
their
current
and
potential
applications,
future
directions
for
field.
possess
complex
architecture
containing
various
neural
cell
types,
synapses,
myelination.
They
have
been
utilized
toxicology
testing,
disease
modeling,
infection
studies,
personalized
medicine,
gene-environment
interaction
studies.
An
emerging
concept
termed
Organoid
Intelligence
(OI)
combines
with
artificial
intelligence
generate
learning
memory,
goals
modeling
cognition
enabling
biological
computing
applications.
allow
neuroscience
studies
not
previously
achievable
traditional
techniques,
transform
drug
development,
understanding
brain
development
disorders.
The
aspirational
vision
OI
parallels
origins
intelligence,
efforts
underway
map
a
roadmap
toward
its
realization.
In
summary,
constitute
disruptive
technology
is
rapidly
advancing
gaining
traction
across
multiple
disciplines.
Molecular Biomedicine,
Journal Year:
2024,
Volume and Issue:
5(1)
Published: Feb. 12, 2024
Abstract
Cancer
is
associated
with
a
high
degree
of
heterogeneity,
encompassing
both
inter-
and
intra-tumor
along
considerable
variability
in
clinical
response
to
common
treatments
across
patients.
Conventional
models
for
tumor
research,
such
as
vitro
cell
cultures
vivo
animal
models,
demonstrate
significant
limitations
that
fall
short
satisfying
the
research
requisites.
Patient-derived
organoids,
which
recapitulate
structures,
specific
functions,
molecular
characteristics,
genomics
alterations
expression
profiles
primary
tumors.
They
have
been
efficaciously
implemented
illness
portrayal,
mechanism
exploration,
high-throughput
drug
screening
assessment,
discovery
innovative
therapeutic
targets
potential
compounds,
customized
treatment
regimen
cancer
In
contrast
conventional
organoids
offer
an
intuitive,
dependable,
efficient
model
by
conserving
phenotypic,
genetic
diversity,
mutational
attributes
originating
tumor.
Nevertheless,
organoid
technology
also
confronts
bottlenecks
challenges,
how
comprehensively
reflect
microenvironment,
angiogenesis,
reduce
costs,
establish
standardized
construction
processes
while
retaining
reliability.
This
review
extensively
examines
use
techniques
fundamental
precision
medicine.
It
emphasizes
importance
patient-derived
biobanks
development,
screening,
safety
evaluation,
personalized
Additionally,
it
evaluates
application
experimental
better
understand
mechanisms
The
intent
this
explicate
significance
present
new
avenues
future
research.
The EMBO Journal,
Journal Year:
2023,
Volume and Issue:
42(22)
Published: Oct. 16, 2023
The
establishment
and
maintenance
of
apical-basal
polarity
is
a
fundamental
step
in
brain
development,
instructing
the
organization
neural
progenitor
cells
(NPCs)
developing
cerebral
cortex.
Particularly,
basally
located
extracellular
matrix
(ECM)
crucial
for
this
process.
In
vitro,
epithelial
polarization
can
be
achieved
via
endogenous
ECM
production,
or
exogenous
supplementation.
While
neuroepithelial
development
recapitulated
organoids,
effects
different
sources
tissue
morphogenesis
remain
underexplored.
Here,
we
show
that
exposure
to
solubilized
basement
membrane
substrate,
Matrigel,
at
early
stages
causes
rapid
rearrangement
architecture.
cultures
exposed
pure
components
unexposed
any
ECM,
acquisition
slower
driven
by
production.
After
onset
neurogenesis,
architecture
neuronal
differentiation
are
largely
independent
initial
source,
but
Matrigel
has
long-lasting
on
patterning.
These
results
advance
knowledge
mechanisms
exogenously
endogenously
guided
morphogenesis,
demonstrating
self-sustainability
processes.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Nov. 28, 2023
Abstract
Pluripotent
stem
cell
(PSC)-derived
human
brain
organoids
enable
the
study
of
development
in
vitro.
Typically,
fate
PSCs
is
guided
into
subsequent
specification
steps
through
static
medium
switches.
In
vivo,
morphogen
gradients
are
critical
for
proper
and
determine
specification,
associated
defects
result
neurodevelopmental
disorders.
Here,
we
show
that
initiating
neural
induction
a
temporal
stepwise
gradient
guides
generation
composed
single,
self-organized
apical-out
neuroepithelium,
termed
ENOs
(expanded
neuroepithelium
organoids).
This
at
odds
with
standard
organoid
protocols
which
multiple
independent
units
(rosettes)
formed.
We
find
prolonged,
decreasing
TGF-β
signaling
determining
factor
ENO
formation
allows
an
extended
phase
expansion.
In-depth
characterization
reveals
display
improved
cellular
morphology
tissue
architectural
features
resemble
vivo
development,
including
expanded
germinal
zones.
Consequently,
cortical
enhanced
ENOs.
constitute
platform
to
early
events
allow
interrogation
complex
relationship
between
architecture
states
shaping
developing
brain.
