Biology,
Год журнала:
2022,
Номер
11(2), С. 316 - 316
Опубликована: Фев. 16, 2022
In
vitro
multielectrode
array
(MEA)
systems
are
increasingly
used
as
higher-throughput
platforms
for
functional
phenotyping
studies
of
neurons
in
induced
pluripotent
stem
cell
(iPSC)
disease
models.
While
MEA
generate
large
amounts
spatiotemporal
activity
data
from
networks
iPSC-derived
neurons,
the
downstream
analysis
and
interpretation
such
high-dimensional
often
pose
a
significant
challenge
to
researchers.
this
review,
we
examine
how
technology
is
currently
deployed
iPSC
modeling
neurodevelopmental
disorders.
We
first
highlight
strengths
by
reviewing
history
its
development
original
scientific
questions
MEAs
were
intended
answer.
Methods
generating
patient
astrocytes
co-cultures
summarized.
then
discuss
challenges
associated
with
context,
present
novel
computational
methods
better
interpret
network
data.
end
suggesting
best
practices
presenting
research
publications,
propose
that
creation
public
repository
enable
collaborative
sharing
would
be
great
benefit
community.
Genome Research,
Год журнала:
2021,
Номер
32(1), С. 71 - 84
Опубликована: Дек. 28, 2021
Astrocytes
contribute
to
motor
neuron
death
in
amyotrophic
lateral
sclerosis
(ALS),
but
whether
they
adopt
deleterious
features
consistent
with
inflammatory
reactive
states
remains
incompletely
resolved.
To
identify
ALS
human
induced
pluripotent
stem
cell
(hiPSC)–derived
astrocytes,
we
examined
transcriptomics,
proteomics,
and
glutamate
uptake
VCP
-mutant
astrocytes.
We
complemented
this
by
examining
other
mutations
models
using
a
systematic
meta-analysis
of
all
publicly-available
astrocyte
sequencing
data,
which
included
hiPSC-derived
astrocytes
carrying
SOD1
,
C9orf72
FUS
gene
as
well
mouse
G93A
mutation,
Tardbp
deletion,
Tmem259
(also
known
membralin)
deletion.
were
characterized
up-regulation
genes
involved
the
extracellular
matrix,
endoplasmic
reticulum
stress,
immune
response
down-regulation
synaptic
integrity,
uptake,
neuronal
support
processes.
activation
TGFB,
Wnt,
hypoxia
signaling
pathways
both
hiPSC
changes
positively
correlate
TNF,
IL1A,
complement
pathway
component
C1q-treated
significant
overlap
differentially
expressed
genes.
By
contrasting
protective
including
middle
cerebral
artery
occlusion
spinal
cord
injury,
uncover
cluster
changing
opposing
directions,
may
represent
down-regulated
homeostatic
up-regulated
These
observations
indicate
that
augment
processes
while
concomitantly
suppressing
supporting
mechanisms,
thus
resembling
offering
potential
therapeutic
targets.
Biology,
Год журнала:
2022,
Номер
11(2), С. 316 - 316
Опубликована: Фев. 16, 2022
In
vitro
multielectrode
array
(MEA)
systems
are
increasingly
used
as
higher-throughput
platforms
for
functional
phenotyping
studies
of
neurons
in
induced
pluripotent
stem
cell
(iPSC)
disease
models.
While
MEA
generate
large
amounts
spatiotemporal
activity
data
from
networks
iPSC-derived
neurons,
the
downstream
analysis
and
interpretation
such
high-dimensional
often
pose
a
significant
challenge
to
researchers.
this
review,
we
examine
how
technology
is
currently
deployed
iPSC
modeling
neurodevelopmental
disorders.
We
first
highlight
strengths
by
reviewing
history
its
development
original
scientific
questions
MEAs
were
intended
answer.
Methods
generating
patient
astrocytes
co-cultures
summarized.
then
discuss
challenges
associated
with
context,
present
novel
computational
methods
better
interpret
network
data.
end
suggesting
best
practices
presenting
research
publications,
propose
that
creation
public
repository
enable
collaborative
sharing
would
be
great
benefit
community.