Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation
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.
Язык: Английский
Neural circuit-selective, multiplexed pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 8, 2024
Selective
manipulation
of
neural
circuits
using
optogenetics
and
chemogenetics
holds
great
translational
potential
but
requires
genetic
access
to
neurons.
Here,
we
demonstrate
a
general
framework
for
identifying
tool-independent,
pharmacological
strategies
circuit-selective
modulation.
We
developed
an
economically
accessible
calcium
imaging-based
approach
large-scale
scans
endogenous
receptor-mediated
activity.
As
testbed
this
approach,
used
the
mouse
locus
coeruleus
due
combination
its
widespread,
modular
efferent
circuitry
wide
variety
endogenously
expressed
GPCRs.
Using
machine
learning-based
action
deconvolution
retrograde
tracing,
identified
agonist
cocktail
that
selectively
inhibits
medial
prefrontal
cortex-projecting
Язык: Английский
Integrating Spatially‐Resolved Transcriptomics Data Across Tissues and Individuals: Challenges and Opportunities
Small Methods,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 11, 2025
Advances
in
spatially-resolved
transcriptomics
(SRT)
technologies
have
propelled
the
development
of
new
computational
analysis
methods
to
unlock
biological
insights.
The
lowering
cost
SRT
data
generation
presents
an
unprecedented
opportunity
create
large-scale
spatial
atlases
and
enable
population-level
investigation,
integrating
across
multiple
tissues,
individuals,
species,
or
phenotypes.
Here,
unique
challenges
are
described
integration,
where
analytic
impact
varying
resolutions
is
characterized
explored.
A
succinct
review
spatially-aware
integration
strategies
provided.
Exciting
opportunities
advance
algorithms
amenable
atlas-scale
datasets
along
with
standardized
preprocessing
methods,
leading
improved
sensitivity
reproducibility
future
further
highlighted.
Язык: Английский
Regenerating Locus Coeruleus‐Norepinephrine (LC‐NE) Function: A Novel Approach for Neurodegenerative Diseases
Cell Proliferation,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 28, 2025
ABSTRACT
Pathological
changes
in
the
locus
coeruleus‐norepinephrine
(LC‐NE)
neurons,
major
source
of
norepinephrine
(NE,
also
known
as
noradrenaline)
brain,
are
evident
during
early
stages
neurodegenerative
diseases
(ND).
Research
on
both
human
and
animal
models
have
highlighted
therapeutic
potential
targeting
LC‐NE
system
to
mitigate
progression
ND
alleviate
associated
psychiatric
symptoms.
However,
widespread
degeneration
presents
a
significant
challenge
for
direct
intervention
ND.
Recent
advances
regenerative
cell
therapy
offer
promising
new
strategies
treatment.
The
regeneration
from
pluripotent
stem
cells
(PSCs)
could
significantly
broaden
scope
LC‐NE‐based
therapies
In
this
review,
we
delve
into
fundamental
background
physiological
functions
LC‐NE.
Additionally,
systematically
examine
evidence
role
neuropathology
over
recent
years.
Notably,
focus
significance
PSCs‐derived
its
impact
therapy.
A
deeper
understanding
further
investigation
function
pave
way
practical
effective
treatments
Язык: Английский
GABAergic mechanisms in alcohol dependence
International review of neurobiology,
Год журнала:
2024,
Номер
unknown, С. 75 - 123
Опубликована: Янв. 1, 2024
Язык: Английский
Monoaminergic degeneration, cognition, and autonomic symptom trajectory in early Parkinson's disease
Parkinsonism & Related Disorders,
Год журнала:
2024,
Номер
127, С. 107086 - 107086
Опубликована: Авг. 3, 2024
Язык: Английский
PreTSA: computationally efficient modeling of temporal and spatial gene expression patterns
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 25, 2024
ABSTRACT
Modeling
temporal
and
spatial
gene
expression
patterns
in
large-scale
single-cell
transcriptomics
data
is
a
computationally
intensive
task.
We
present
PreTSA,
method
that
offers
computational
efficiency
modeling
these
applicable
to
comprising
millions
of
cells.
PreTSA
consistently
matches
the
results
state-of-the-art
methods
while
significantly
reducing
time.
provides
unique
solution
for
studying
extremely
large
datasets.
Язык: Английский