Cells,
Год журнала:
2020,
Номер
9(7), С. 1717 - 1717
Опубликована: Июль 17, 2020
The
pro-inflammatory
immune
response
driven
by
microglia
is
a
key
contributor
to
the
pathogenesis
of
several
neurodegenerative
diseases.
Though
research
spans
over
century,
last
two
decades
have
increased
our
understanding
exponentially.
Here,
we
discuss
phenotypic
transformation
from
homeostatic
towards
reactive
microglia,
initiated
specific
ligand
binding
pattern
recognition
receptors
including
toll-like
receptor-4
(TLR4)
or
triggering
expressed
on
myeloid
cells-2
(TREM2),
as
well
signaling
pathways
triggered
such
caspase-mediated
response.
Additionally,
new
disciplines
epigenetics
and
immunometabolism
provided
us
with
more
holistic
view
how
changes
in
DNA
methylation,
microRNAs,
metabolome
may
influence
This
review
aimed
current
knowledge
different
angles,
recent
highlights
role
exosomes
spreading
neuroinflammation
emerging
techniques
positron
emission
tomography
(PET)
scanning
use
human
generated
induced
pluripotent
stem
cells
(iPSCs).
Finally,
also
thoughts
impact
Brain
organoids
are
self-assembled
three-dimensional
aggregates
generated
from
pluripotent
stem
cells
with
cell
types
and
cytoarchitectures
that
resemble
the
embryonic
human
brain.
As
such,
they
have
emerged
as
novel
model
systems
can
be
used
to
investigate
brain
development
disorders.
Although
mimic
many
key
features
of
early
at
molecular,
cellular,
structural
functional
levels,
some
aspects
development,
such
formation
distinct
cortical
neuronal
layers,
gyrification,
establishment
complex
circuitry,
not
fully
recapitulated.
Here,
we
summarize
recent
advances
in
organoid
methodologies
discuss
their
applications
disease
modeling.
In
addition,
compare
current
brain,
highlighting
currently
cannot
recapitulated,
perspectives
for
advancing
technologies
expand
applications.
Nature Communications,
Год журнала:
2018,
Номер
9(1)
Опубликована: Окт. 3, 2018
Cerebral
organoids
are
3D
stem
cell-derived
models
that
can
be
utilized
to
study
the
human
brain.
The
current
consensus
is
cerebral
consist
of
cells
derived
from
neuroectodermal
lineage.
This
limits
their
value
and
applicability,
as
mesodermal-derived
microglia
important
players
in
neural
development
disease.
Remarkably,
here
we
show
innately
develop
within
a
organoid
model
display
characteristic
ramified
morphology.
transcriptome
response
inflammatory
stimulation
these
organoid-grown
closely
mimic
adult
acutely
isolated
post
mortem
brain
tissue.
In
addition,
mediate
phagocytosis
synaptic
material
detected
inside
them.
all,
our
characterizes
microglia-containing
represents
valuable
tool
for
studying
interplay
between
microglia,
macroglia,
neurons
Stem Cell Reports,
Год журнала:
2017,
Номер
8(6), С. 1727 - 1742
Опубликована: Июнь 1, 2017
Microglia
are
increasingly
implicated
in
brain
pathology,
particularly
neurodegenerative
disease,
with
many
genes
Alzheimer's,
Parkinson's,
and
motor
neuron
disease
expressed
microglia.
There
is,
therefore,
a
need
for
authentic,
efficient
vitro
models
to
study
human
microglial
pathological
mechanisms.
originate
from
the
yolk
sac
as
MYB-independent
macrophages,
migrating
into
developing
complete
differentiation.
Here,
we
recapitulate
ontogeny
by
highly
differentiation
of
embryonic
iPSC-derived
macrophages
then
co-culture
them
cortical
neurons.
Co-cultures
retain
neuronal
maturity
functionality
weeks.
Co-culture
microglia
express
key
microglia-specific
markers
disease-relevant
genes,
develop
dynamic
ramifications,
phagocytic.
Upon
activation
they
become
more
ameboid,
releasing
multiple
microglia-relevant
cytokines.
Importantly,
downregulate
pathogen-response
pathways,
upregulate
homeostatic
function
promote
anti-inflammatory
pro-remodeling
cytokine
response
than
corresponding
monocultures,
demonstrating
that
co-cultures
preferable
modeling
authentic
physiology.
