Excitatory Cortical Neurons from CDKL5 Deficiency Disorder Patient-Derived Organoids Show Early Hyperexcitability Not Identified in Neurogenin2 Induced Neurons
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 11, 2024
CDKL5
deficiency
disorder
(CDD)
is
a
rare
developmental
and
epileptic
encephalopathy
resulting
from
variants
in
cyclin-dependent
kinase-like
5
(CDKL5)
that
lead
to
impaired
kinase
activity
or
loss
of
function.
CDD
one
the
most
common
genetic
etiologies
identified
epilepsy
cohorts.
To
study
how
impact
human
neuronal
activity,
gene
expression
morphology,
patient-derived
induced
pluripotent
stem
cells
their
isogenic
controls
were
differentiated
into
excitatory
neurons
using
either
an
NGN2
induction
protocol
guided
cortical
organoid
differentiation.
Patient-derived
both
differentiation
paradigms
had
decreased
phosphorylated
EB2,
known
molecular
target
CDKL5.
Induced
showed
no
detectable
differences
between
cases
network
multielectrode
array,
MAP2+
neurite
length,
only
two
genes
differentially
expressed.
However,
increased
synchrony
weighted
mean
firing
rate
on
array
within
first
month
maturation.
lower
HS3ST1,
which
may
change
extracellular
matrix
around
synapse
contribute
hyperexcitability.
Similar
neurons,
there
length
across
patient-control
cell
lines.
have
poor
specification
while
derived
expressed
markers,
suggesting
changes
excitability
are
specific
neurons.
Examining
mechanisms
early
hyperexcitability
promising
avenue
for
identification
therapeutics.
Язык: Английский
In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between
Biomedicines,
Год журнала:
2024,
Номер
12(12), С. 2714 - 2714
Опубликована: Ноя. 27, 2024
Cardiovascular
disease
comprises
a
group
of
disorders
affecting
or
originating
within
tissues
and
organs
the
cardiovascular
system;
most,
if
not
all,
will
eventually
result
in
cardiomyocyte
dysfunction
death,
negatively
impacting
cardiac
function.
Effective
models
are
thus
important
for
understanding
crucial
aspects
progression,
while
recent
advancements
stem
cell
biology
have
allowed
use
populations
to
derive
such
models.
These
include
three-dimensional
(3D)
as
cell-based
embryos
(SCME)
well
organoids,
many
which
frequently
derived
from
embryoid
bodies
(EB).
Not
only
can
they
recapitulate
3D
form
function,
but
developmental
programs
governing
self-organization
into
more
complex
well.
Many
different
organoids
SCME
constructs
been
generated
years
recreate
tissue
that
give
rise
its
cellular
composition
unique
morphology.
It
is
purpose
this
narrative
literature
review
describe
summarize
recently
organoid
their
recapitulation
genetic
acquired
disease.
Owing
examined,
focus
on
injury
associated
with
embryonic/fetal
tissues.
Язык: Английский