Recent
advancements
in
single-cell
technologies
have
led
to
rapid
developments
the
construction
of
cell
atlases.
These
atlases
potential
provide
detailed
information
about
every
type
different
organisms,
enabling
characterization
cellular
diversity
at
level.
Global
efforts
developing
comprehensive
profound
implications
for
both
basic
research
and
clinical
applications.
This
review
provides
a
broad
overview
dynamics
across
various
biological
systems.
In
addition,
incorporation
machine
learning
techniques
into
atlas
analyses
opens
up
exciting
prospects
field
integrative
biology.
Cell,
Год журнала:
2023,
Номер
186(20), С. 4365 - 4385.e27
Опубликована: Сен. 1, 2023
Alzheimer's
disease
(AD)
is
the
most
common
cause
of
dementia
worldwide,
but
molecular
and
cellular
mechanisms
underlying
cognitive
impairment
remain
poorly
understood.
To
address
this,
we
generated
a
single-cell
transcriptomic
atlas
aged
human
prefrontal
cortex
covering
2.3
million
cells
from
postmortem
brain
samples
427
individuals
with
varying
degrees
AD
pathology
impairment.
Our
analyses
identified
AD-pathology-associated
alterations
shared
between
excitatory
neuron
subtypes,
revealed
coordinated
increase
cohesin
complex
DNA
damage
response
factors
in
neurons
oligodendrocytes,
uncovered
genes
pathways
associated
high
function,
dementia,
resilience
to
pathology.
Furthermore,
selectively
vulnerable
somatostatin
inhibitory
subtypes
depleted
AD,
discovered
two
distinct
groups
that
were
more
abundant
preserved
function
late
life,
link
Cell stem cell,
Год журнала:
2023,
Номер
30(2), С. 120 - 136
Опубликована: Фев. 1, 2023
Adult
hippocampal
neurogenesis
(AHN)
drops
sharply
during
early
stages
of
Alzheimer's
disease
(AD),
via
unknown
mechanisms,
and
correlates
with
cognitive
status
in
AD
patients.
Understanding
AHN
regulation
could
provide
a
framework
for
innovative
pharmacological
interventions.
We
here
combine
molecular,
behavioral,
clinical
data
critically
discuss
the
multicellular
complexity
niche
relation
to
pathophysiology.
further
present
roadmap
toward
better
understanding
role
by
probing
promises
caveats
latest
technological
advancements
field
addressing
conceptual
methodological
challenges
ahead.
Nature,
Год журнала:
2024,
Номер
632(8026), С. 858 - 868
Опубликована: Июль 24, 2024
Abstract
Alzheimer’s
disease
is
the
leading
cause
of
dementia
worldwide,
but
cellular
pathways
that
underlie
its
pathological
progression
across
brain
regions
remain
poorly
understood
1–3
.
Here
we
report
a
single-cell
transcriptomic
atlas
six
different
in
aged
human
brain,
covering
1.3
million
cells
from
283
post-mortem
samples
48
individuals
with
and
without
disease.
We
identify
76
cell
types,
including
region-specific
subtypes
astrocytes
excitatory
neurons
an
inhibitory
interneuron
population
unique
to
thalamus
distinct
canonical
subclasses.
vulnerable
populations
are
depleted
specific
disease,
provide
evidence
Reelin
signalling
pathway
involved
modulating
vulnerability
these
neurons.
develop
scalable
method
for
discovering
gene
modules,
which
use
cell-type-specific
modules
altered
annotate
differences
associated
diverse
variables.
astrocyte
program
cognitive
resilience
pathology,
tying
choline
metabolism
polyamine
biosynthesis
preserved
function
late
life.
Together,
our
study
develops
regional
ageing
provides
insights
into
vulnerability,
response
pathology.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 14, 2024
Abstract
Human
hippocampal
organoids
(hHOs)
derived
from
human
induced
pluripotent
stem
cells
(hiPSCs)
have
emerged
as
promising
models
for
investigating
neurodegenerative
disorders,
such
schizophrenia
and
Alzheimer’s
disease.
However,
obtaining
the
electrical
information
of
these
free-floating
in
a
noninvasive
manner
remains
challenge
using
commercial
multi-electrode
arrays
(MEAs).
The
three-dimensional
(3D)
MEAs
developed
recently
acquired
only
few
neural
signals
due
to
limited
channel
numbers.
Here,
we
report
cyborg
organoid
(cyb-organoid)
platform
coupling
liquid
metal-polymer
conductor
(MPC)-based
mesh
neuro-interface
with
hHOs.
MPC
(mMPC)
integrates
128-channel
multielectrode
distributed
on
small
surface
area
(~2*2
mm).
Stretchability
(up
500%)
flexibility
mMPC
enable
its
attachment
Furthermore,
show
that
under
Wnt3a
SHH
activator
induction,
hHOs
produce
HOPX
+
PAX6
progenitors
ZBTB20
PROX1
dentate
gyrus
(DG)
granule
neurons.
transcriptomic
signatures
reveal
high
similarity
developing
hippocampus.
We
successfully
detect
activities
via
this
cyb-organoid.
Compared
traditional
planar
devices,
our
non-invasive
offers
an
adaptor
recording
3D
models.
Nature Neuroscience,
Год журнала:
2025,
Номер
28(2), С. 415 - 430
Опубликована: Янв. 6, 2025
Abstract
The
mammalian
dentate
gyrus
(DG)
is
involved
in
certain
forms
of
learning
and
memory,
DG
dysfunction
has
been
implicated
age-related
diseases.
Although
neurogenic
potential
maintained
throughout
life
the
as
neural
stem
cells
(NSCs)
continue
to
generate
new
neurons,
neurogenesis
decreases
with
advancing
age,
implications
for
cognitive
decline
disease.
In
this
study,
we
used
single-cell
RNA
sequencing
characterize
transcriptomic
signatures
their
surrounding
niche,
identifying
molecular
changes
associated
aging
from
activation
quiescent
NSCs
maturation
fate-committed
progeny.
By
integrating
spatial
transcriptomics
data,
identified
regional
invasion
inflammatory
into
hippocampus
age
show
here
that
early-onset
neuroinflammation
activity.
Our
data
reveal
lifelong
dynamics
niche
provide
a
powerful
resource
understand
alterations
hippocampus.
Nature Neuroscience,
Год журнала:
2024,
Номер
27(6), С. 1064 - 1074
Опубликована: Май 20, 2024
Abstract
Ancestral
differences
in
genomic
variation
affect
the
regulation
of
gene
expression;
however,
most
expression
studies
have
been
limited
to
European
ancestry
samples
or
adjusted
identify
ancestry-independent
associations.
Here,
we
instead
examined
impact
genetic
on
and
DNA
methylation
postmortem
brain
tissue
admixed
Black
American
neurotypical
individuals
ancestry-dependent
contributions.
Ancestry-associated
differentially
expressed
genes
(DEGs),
transcripts
networks,
while
notably
not
implicating
neurons,
are
enriched
for
related
immune
response
vascular
explain
up
26%
heritability
ischemic
stroke,
27%
Parkinson
disease
30%
Alzheimer’s
disease.
DEGs
also
show
general
enrichment
diverse
immune-related
traits
but
depletion
psychiatric-related
traits.
We
compared
non-Hispanic
white
Americans,
confirming
ancestry-associated
DEGs.
Our
results
delineate
extent
which
affects
human
implications
illness
risk.
Cell Reports,
Год журнала:
2025,
Номер
44(2), С. 115300 - 115300
Опубликована: Фев. 1, 2025
The
dentate
gyrus
of
the
hippocampus
is
important
for
many
cognitive
functions,
including
learning,
memory,
and
mood.
Here,
we
present
transcriptome-wide
spatial
gene
expression
maps
human
investigate
age-associated
changes
across
lifespan.
Genes
associated
with
neurogenesis
extracellular
matrix
are
enriched
in
infants
decline
throughout
development
maturation.
Following
infancy,
inhibitory
neuron
markers
increase,
cellular
proliferation
decrease.
We
also
identify
spatio-molecular
signatures
that
support
existing
evidence
protracted
maturation
granule
cells
during
adulthood
increases
neuroinflammation-related
expression.
Our
findings
notion
hippocampal
neurogenic
niche
undergoes
major
following
infancy
molecular
regulators
brain
aging
glial-
neuropil-enriched
tissue.
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Фев. 21, 2025
Normal
aging
alters
brain
functions
and
phenotypes.
However,
it
is
not
well
understood
how
astrocytes
are
impacted
by
aging,
nor
they
contribute
to
neuronal
dysfunction
disease
risk
as
organisms
age.
Here,
we
examine
the
transcriptional,
cell
biology,
functional
differences
in
across
normal
aging.
Astrocytes
at
baseline
heterogenous,
responsive
their
environments,
critical
regulators
of
microenvironments
function.
With
increasing
age,
adopt
different
immune-related
senescence-associated
states,
which
relate
organelle
loss
homeostasis
maintenance,
both
autonomously
non-cell
autonomously.
These
perturbed
states
increasingly
associated
with
age-related
onset
neurodegeneration,
suggesting
that
astrocyte
a
compelling
target
for
future
manipulation
prevention
disease.
