Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 3, 2024
Traumatic
brain
injury
leads
to
a
highly
orchestrated
immune-
and
glial
cell
response
partially
responsible
for
long-lasting
disability
the
development
of
secondary
neurodegenerative
diseases.
A
holistic
understanding
mechanisms
controlling
responses
specific
types
their
crosstalk
is
required
develop
an
efficient
strategy
better
regeneration.
Here,
we
combine
spatial
single-cell
transcriptomics
chart
transcriptomic
signature
injured
male
murine
cerebral
cortex,
identify
states
different
cells
contributing
this
signature.
Interestingly,
distinct
share
large
fraction
injury-regulated
genes,
including
inflammatory
programs
downstream
innate
immune-associated
pathways
Cxcr3
Tlr1/2.
Systemic
manipulation
these
decreases
reactivity
state
associated
with
poor
The
functional
relevance
discovered
shared
highlights
importance
our
resource
enabling
comprehensive
analysis
early
events
after
injury.
ACS Nano,
Год журнала:
2024,
Номер
18(16), С. 10738 - 10757
Опубликована: Апрель 12, 2024
Biomolecular
condensates
play
important
roles
in
a
wide
array
of
fundamental
biological
processes,
such
as
cellular
compartmentalization,
regulation,
and
other
biochemical
reactions.
Since
their
discovery
first
observations,
an
extensive
expansive
library
tools
has
been
developed
to
investigate
various
aspects
properties,
encompassing
structural
compositional
information,
material
evolution
throughout
the
life
cycle
from
formation
eventual
dissolution.
This
Review
presents
overview
expanded
set
methods
that
researchers
use
probe
properties
biomolecular
across
diverse
scales
length,
concentration,
stiffness,
time.
In
particular,
we
review
recent
years'
exciting
development
label-free
techniques
methodologies.
We
broadly
organize
into
3
categories:
(1)
imaging-based
techniques,
transmitted-light
microscopy
(TLM)
Brillouin
(BM),
(2)
force
spectroscopy
atomic
(AFM)
optical
tweezer
(OT),
(3)
microfluidic
platforms
emerging
technologies.
point
out
tools'
key
opportunities,
challenges,
future
perspectives
analyze
correlative
potential
well
compatibility
with
techniques.
Additionally,
namely,
differential
dynamic
(DDM)
interferometric
scattering
(iSCAT),
have
huge
for
applications
studying
condensates.
Finally,
highlight
how
some
these
can
be
translated
diagnostics
therapy
purposes.
hope
this
serves
useful
guide
new
field
aids
advancing
biophysical
study
Acta Neuropathologica Communications,
Год журнала:
2023,
Номер
11(1)
Опубликована: Май 22, 2023
Abstract
The
myelinated
white
matter
tracts
of
the
central
nervous
system
(CNS)
are
essential
for
fast
transmission
electrical
impulses
and
often
differentially
affected
in
human
neurodegenerative
diseases
across
CNS
region,
age
sex.
We
hypothesize
that
this
selective
vulnerability
is
underpinned
by
physiological
variation
glia.
Using
single
nucleus
RNA
sequencing
post-mortem
samples
from
brain,
cerebellum
spinal
cord
subsequent
tissue-based
validation
we
found
substantial
glial
heterogeneity
with
tissue
region:
identified
region-specific
oligodendrocyte
precursor
cells
(OPCs)
retain
developmental
origin
markers
into
adulthood,
distinguishing
them
mouse
OPCs.
Region-specific
OPCs
give
rise
to
similar
populations,
however
oligodendrocytes
exhibit
such
as
SKAP2
which
associated
increased
myelin
production
a
population
particularly
equipped
producing
long
thick
sheaths
based
on
expression
genes/proteins
HCN2
.
Spinal
microglia
more
activated
phenotype
compared
brain
microglia,
suggesting
pro-inflammatory
environment,
difference
intensifies
age.
Astrocyte
gene
correlates
strongly
however,
astrocytes
do
not
show
state
region
or
Across
all
glia,
sex
differences
subtle
but
consistent
protein-folding
genes
male
donors
hints
at
pathways
may
contribute
disease
susceptibility.
These
findings
consider
understanding
pathologies
developing
tailored
therapeutic
strategies.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 17, 2024
Spared
regions
of
the
damaged
central
nervous
system
undergo
dynamic
remodeling
and
exhibit
a
remarkable
potential
for
therapeutic
exploitation.
Here,
lesion-remote
astrocytes
(LRAs),
which
interact
with
viable
neurons,
glia
neural
circuitry,
reactive
transformations
whose
molecular
functional
properties
are
poorly
understood.
Using
multiple
transcriptional
profiling
methods,
we
interrogated
LRAs
from
spared
mouse
spinal
cord
following
traumatic
injury
(SCI).
We
show
that
acquire
spectrum
molecularly
distinct,
neuroanatomically
restricted
reactivity
states
evolve
after
SCI.
identify
transcriptionally
unique
in
degenerating
white
matter
direct
specification
function
local
microglia
clear
lipid-rich
myelin
debris
to
promote
tissue
repair.
Fueling
this
LRA
adaptation
is
Ccn1
,
encodes
secreted
matricellular
protein.
Loss
astrocyte
CCN1
leads
excessive,
aberrant
activation
(i)
abnormal
specification,
(ii)
dysfunctional
processing,
(iii)
impaired
lipid
metabolism,
culminating
blunted
clearance
attenuated
neurological
recovery
-expressing
specifically
induced
by
damage
generated
diverse
demyelinating
disorders
human,
pointing
their
fundamental,
evolutionarily
conserved
role
Our
findings
assume
regionally
divergent
adaptations
context-specific
triggers
influence
disorder
outcome.
Astrocytes
tile
(CNS)
where
they
serve
vital
roles
uphold
healthy
function,
including
regulation
synapse
development,
buffering
neurotransmitters
ions,
provision
metabolic
substrates
1
.
In
response
CNS
insults,
disorder-context
specific
collectively
referred
as
2-5
The
characteristics
distinct
incompletely
mechanisms
through
arise,
how
or
resolve
over
time,
consequences
cell
progression
remain
enigmatic.
Immediately
adjacent
lesions,
border-forming
(BFAs)
reprogramming
proliferation
form
neuroprotective
barrier
restricts
inflammation
supports
axon
regeneration
6-9
Beyond
lesion,
but
injured
varying
degrees
synaptic
circuit
progressive
cellular
responses
secondary
have
profound
repair
10,11
Throughout
these
cytoarchitecturally
intact,
injury-reactive
regions,
(LRAs)
intermingle
neurons
glia,
little
no
proliferation,
hypertrophy
7,12,13
grossly
undefined.
Therapeutically
harnessing
will
require
clearer
understanding
accompanying
landscape.
leveraged
integrative
methodologies
spatiotemporally
resolved,
within
cord.
Computational
modeling
LRA-mediated
heterotypic
interactions,
astrocyte-specific
conditional
gene
deletion,
models
acute
chronic
degeneration
were
used
interrogate
newly
identified
degeneration-reactive
subtype.
define
state
its
governing
Old
age
is
associated
with
a
decline
in
cognitive
function
and
an
increase
neurodegenerative
disease
risk1.
Brain
ageing
complex
accompanied
by
many
cellular
changes2.
Furthermore,
the
influence
that
aged
cells
have
on
neighbouring
how
this
contributes
to
tissue
unknown.
More
generally,
tools
systematically
address
question
tissues
not
yet
been
developed.
Here
we
generate
spatially
resolved
single-cell
transcriptomics
brain
atlas
of
4.2
million
from
20
distinct
ages
across
adult
lifespan
two
rejuvenating
interventions—exercise
partial
reprogramming.
We
build
spatial
clocks,
machine
learning
models
trained
atlas,
identify
cell-type-specific
transcriptomic
fingerprints
ageing,
rejuvenation
disease,
including
for
rare
cell
types.
Using
clocks
deep
learning,
find
T
cells,
which
increasingly
infiltrate
age,
marked
pro-ageing
proximity
effect
cells.
Surprisingly,
neural
stem
strong
pro-rejuvenating
also
potential
mediators
their
neighbours.
These
results
suggest
types
can
potent
neighbours
could
be
targeted
counter
ageing.
Spatial
represent
useful
tool
studying
cell–cell
interactions
contexts
should
allow
scalable
assessment
efficacy
interventions
disease.
A
map
mouse
at
different
reveals
signatures
effects
Neuroglia,
Год журнала:
2025,
Номер
6(1), С. 2 - 2
Опубликована: Янв. 4, 2025
Microglia
are
exceptionally
dynamic
resident
innate
immune
cells
within
the
central
nervous
system,
existing
on
a
continuum
of
morphologies
and
functions
throughout
their
lifespan.
They
play
vital
roles
in
response
to
injuries
infections,
clearing
cellular
debris,
maintaining
neural
homeostasis
development.
Emerging
research
suggests
that
microglia
strongly
influenced
by
biological
factors,
including
sex,
developmental
stage,
local
environment.
This
review
synthesizes
findings
sex
differences
microglial
morphology
function
key
brain
regions,
frontal
cortex,
hippocampus,
amygdala,
hypothalamus,
basal
ganglia,
cerebellum,
across
Where
available,
we
examine
how
gonadal
hormones
influence
these
characteristics.
Additionally,
highlight
limitations
relying
solely
infer
underscore
need
for
comprehensive,
multimodal
approaches
guide
future
research.
Ultimately,
this
aims
advance
dialogue
spatiotemporally
heterogeneous
implications
vulnerability
neurological
psychiatric
disorders.
