Cells,
Journal Year:
2023,
Volume and Issue:
12(4), P. 625 - 625
Published: Feb. 15, 2023
Progressive
accumulation
of
α-Synuclein
(αSyn)
in
Lewy
bodies
(LBs)
and
loss
dopaminergic
(DA)
neurons
are
the
hallmark
pathological
features
Parkinson’s
disease
(PD).
Although
currently
available
vitro
vivo
models
have
provided
crucial
information
about
PD
pathogenesis,
mechanistic
link
between
progressive
αSyn
into
LBs
DA
is
still
unclear.
To
address
this,
it
critical
to
model
LB
formation
neuron
loss,
two
key
neuropathological
aspects
PD,
a
relevant
system.
In
this
study,
we
developed
human
midbrain-like
organoid
(hMBO)
PD.
We
demonstrated
that
hMBOs
generated
from
induced
pluripotent
stem
cells
(hiPSCs),
derived
familial
(fPD)
patient
carrying
gene
(SNCA)
triplication
accumulate
over
time.
These
cytoplasmic
inclusions
spatially
morphologically
resembled
diverse
stages
were
composed
markers
LBs.
Importantly,
was
paralleled
by
elevated
apoptosis.
The
study
will
complement
existing
provide
unique
platform
spatiotemporal
events
governing
their
relation
with
neurodegeneration.
Furthermore,
also
be
beneficial
for
screening
development
therapeutic
compounds.
Organs-on-chips
(OoCs)
are
systems
containing
engineered
or
natural
miniature
tissues
grown
inside
microfluidic
chips.
To
better
mimic
human
physiology,
the
chips
designed
to
control
cell
microenvironments
and
maintain
tissue-specific
functions.
Combining
advances
in
tissue
engineering
microfabrication,
OoCs
have
gained
interest
as
a
next-generation
experimental
platform
investigate
pathophysiology
effect
of
therapeutics
body.
There
many
examples
there
applications,
making
it
difficult
for
new
researchers
understand
what
makes
one
OoC
more
suited
an
application
than
another.
This
Primer
is
intended
give
introduction
aspects
that
need
be
considered
when
developing
application-specific
OoC.
The
covers
guiding
principles
considerations
design,
fabricate
operate
OoC,
well
subsequent
assaying
techniques
extract
biological
information
from
devices.
Alongside
this
discussion
current
future
applications
technology,
inform
design
operational
decisions
during
implementation
systems.
with
aim
mimicking
physiology
range
biomedical
therapeutic
applications.
Leung,
de
Haan
et
al.
report
practical
tips
organ-on-a-chip
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: July 29, 2022
Human
brain
organoids
replicate
much
of
the
cellular
diversity
and
developmental
anatomy
human
brain.
However,
physiology
neuronal
circuits
within
remains
under-explored.
With
high-density
CMOS
microelectrode
arrays
shank
electrodes,
we
captured
spontaneous
extracellular
activity
from
derived
induced
pluripotent
stem
cells.
We
inferred
functional
connectivity
spike
timing,
revealing
a
large
number
weak
connections
skeleton
significantly
fewer
strong
connections.
A
benzodiazepine
increased
uniformity
firing
patterns
decreased
relative
fraction
weakly
connected
edges.
Our
analysis
local
field
potential
demonstrate
that
contain
assemblies
sufficient
size
to
co-activate
generate
potentials
their
collective
transmembrane
currents
phase-lock
spiking
activity.
These
results
point
for
study
neuropsychiatric
diseases,
drug
action,
effects
external
stimuli
upon
networks.
Frontiers in Molecular Neuroscience,
Journal Year:
2021,
Volume and Issue:
14
Published: March 31, 2021
The
SOX
proteins
belong
to
the
superfamily
of
transcription
factors
(TFs)
that
display
properties
both
classical
TFs
and
architectural
components
chromatin.
Since
cloning
Sox/SOX
genes,
remarkable
progress
has
been
made
in
illuminating
their
roles
as
key
players
regulation
multiple
developmental
physiological
processes.
govern
diverse
cellular
processes
during
development,
such
maintaining
pluripotency
stem
cells,
cell
proliferation,
fate
decisions/germ
layer
formation
well
terminal
differentiation
into
tissues
organs.
However,
are
not
limited
development
since
influence
survival,
regeneration,
death
control
homeostasis
adult
tissues.
This
review
summarized
current
knowledge
central
nervous
system
development.
Some
suspend
neural
progenitors
proliferative,
stem-like
state
prevent
differentiation.
function
pioneer
occupy
silenced
target
genes
keep
them
a
poised
for
activation
at
subsequent
stages
At
appropriate
stage
members
maintain
stemness
down-regulated
cells
competent
differentiate,
while
other
take
over
functions
process
Distinct
determine
down-stream
neuronal
glial
Thus,
sequentially
acting
orchestrate
lineage
defining
phenotypes.
In
line
with
crucial
deregulation
specific
activities
is
associated
neurodevelopmental
disorders
(NDDs).
overview
about
link
between
gene
variants
NDDs
presented.
We
outline
neurogenesis
brain
discuss
whether
impaired
neurogenesis,
detected
neurodegenerative
diseases,
could
be
activities.
present
data
regarding
interaction
signaling
pathways
microRNAs
play
Finally,
future
research
directions
will
improve
distinct
various
health
diseases
presented
discussed.
Science Advances,
Journal Year:
2022,
Volume and Issue:
8(33)
Published: Aug. 17, 2022
Brain
organoids
are
important
models
for
mimicking
some
three-dimensional
(3D)
cytoarchitectural
and
functional
aspects
of
the
brain.
Multielectrode
arrays
(MEAs)
that
enable
recording
stimulation
activity
from
electrogenic
cells
offer
notable
potential
interrogating
brain
organoids.
However,
conventional
MEAs,
initially
designed
monolayer
cultures,
limited
contact
area
restricted
to
bottom
3D
Inspired
by
shape
electroencephalography
caps,
we
developed
miniaturized
wafer-integrated
MEA
caps
The
optically
transparent
shells
composed
self-folding
polymer
leaflets
with
conductive
polymer–coated
metal
electrodes.
Tunable
folding
minicaps’
guided
mechanics
simulations
enables
versatile
different
sizes,
validate
feasibility
electrophysiology
400-
600-μm-sized
up
4
weeks
in
response
glutamate
stimulation.
Our
studies
suggest
shell
MEAs
great
high
signal-to-noise
ratio
spatiotemporal
organoid
recording.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: April 26, 2024
The
induced
pluripotent
stem
cell
(iPSC)
technology
has
transformed
in
vitro
research
and
holds
great
promise
to
advance
regenerative
medicine.
iPSCs
have
the
capacity
for
an
almost
unlimited
expansion,
are
amenable
genetic
engineering,
can
be
differentiated
into
most
somatic
types.
been
widely
applied
model
human
development
diseases,
perform
drug
screening,
develop
therapies.
In
this
review,
we
outline
key
developments
iPSC
field
highlight
immense
versatility
of
modeling
therapeutic
applications.
We
begin
by
discussing
pivotal
discoveries
that
revealed
potential
a
nucleus
reprogramming
led
successful
generation
iPSCs.
consider
molecular
mechanisms
dynamics
as
well
numerous
methods
available
induce
pluripotency.
Subsequently,
discuss
various
iPSC-based
cellular
models,
from
mono-cultures
single
type
complex
three-dimensional
organoids,
how
these
models
elucidate
diseases.
use
examples
neurological
disorders,
coronavirus
disease
2019
(COVID-19),
cancer
diversity
disease-specific
phenotypes
modeled
using
iPSC-derived
cells.
also
used
high-throughput
screening
toxicity
studies.
Finally,
process
developing
autologous
allogeneic
therapies
their
alleviate
Nature Biotechnology,
Journal Year:
2023,
Volume and Issue:
41(12), P. 1765 - 1775
Published: May 8, 2023
Abstract
Organoids
generated
from
human
pluripotent
stem
cells
provide
experimental
systems
to
study
development
and
disease,
but
quantitative
measurements
across
different
spatial
scales
molecular
modalities
are
lacking.
In
this
study,
we
multiplexed
protein
maps
over
a
retinal
organoid
time
course
primary
adult
tissue.
We
developed
toolkit
visualize
progenitor
neuron
location,
the
arrangements
of
extracellular
subcellular
components
global
patterning
in
each
addition,
single-cell
transcriptome
chromatin
accessibility
timecourse
dataset
inferred
gene
regulatory
network
underlying
development.
integrated
genomic
data
with
spatially
segmented
nuclei
into
multimodal
atlas
explore
ganglion
cell
(RGC)
neighborhoods,
highlighting
pathways
involved
RGC
death
showing
that
mosaic
genetic
perturbations
organoids
insight
fate
regulation.