Nature,
Год журнала:
2022,
Номер
611(7936), С. 540 - 547
Опубликована: Ноя. 9, 2022
Abstract
A
spinal
cord
injury
interrupts
pathways
from
the
brain
and
brainstem
that
project
to
lumbar
cord,
leading
paralysis.
Here
we
show
spatiotemporal
epidural
electrical
stimulation
(EES)
of
1–3
applied
during
neurorehabilitation
4,5
(EES
REHAB
)
restored
walking
in
nine
individuals
with
chronic
injury.
This
recovery
involved
a
reduction
neuronal
activity
humans
walking.
We
hypothesized
this
unexpected
reflects
activity-dependent
selection
specific
subpopulations
become
essential
for
patient
walk
after
To
identify
these
putative
neurons,
modelled
technological
therapeutic
features
underlying
EES
mice.
single-nucleus
RNA
sequencing
6–9
spatial
transcriptomics
10,11
cords
mice
chart
spatially
resolved
molecular
atlas
then
employed
cell
type
12,13
prioritization
neurons
single
population
excitatory
interneurons
nested
within
intermediate
laminae
emerged.
Although
are
not
required
before
injury,
demonstrate
they
following
Augmenting
phenocopied
enabled
by
,
whereas
ablating
them
prevented
occurs
spontaneously
moderate
thus
identified
recovery-organizing
subpopulation
is
necessary
sufficient
regain
Moreover,
our
methodology
establishes
framework
using
cartography
produce
complex
behaviours.
Neuron,
Год журнала:
2023,
Номер
111(3), С. 328 - 344.e7
Опубликована: Фев. 1, 2023
The
mammalian
spinal
cord
functions
as
a
community
of
cell
types
for
sensory
processing,
autonomic
control,
and
movement.
While
animal
models
have
advanced
our
understanding
cellular
diversity,
characterizing
human
biology
directly
is
important
to
uncover
specialized
features
basic
function
pathology.
Here,
we
present
taxonomy
the
adult
using
single-nucleus
RNA
sequencing
with
spatial
transcriptomics
antibody
validation.
We
identified
29
glial
clusters
35
neuronal
clusters,
organized
principally
by
anatomical
location.
To
demonstrate
relevance
this
resource
disease,
analyzed
motoneurons,
which
degenerate
in
amyotrophic
lateral
sclerosis
(ALS)
other
diseases.
found
that
compared
neurons,
motoneurons
are
defined
genes
related
size,
cytoskeletal
structure,
ALS,
suggesting
molecular
repertoire
underlying
their
selective
vulnerability.
include
web
facilitate
further
investigations
into
biology.
Neuron,
Год журнала:
2023,
Номер
111(23), С. 3745 - 3764.e7
Опубликована: Сен. 29, 2023
Leptomeninges,
consisting
of
the
pia
mater
and
arachnoid,
form
a
connective
tissue
investment
barrier
enclosure
brain.
The
exact
nature
leptomeningeal
cells
has
long
been
debated.
In
this
study,
we
identify
five
molecularly
distinct
fibroblast-like
transcriptomes
in
cerebral
leptomeninges;
link
them
to
anatomically
cell
types
pia,
inner
outer
arachnoid
barrier,
dural
border
layer;
contrast
sixth
transcriptome
present
choroid
plexus
median
eminence.
Newly
identified
transcriptional
markers
enabled
molecular
characterization
responsible
for
adherence
layers
one
another
barrier.
These
also
proved
useful
identifying
features
development,
injury,
repair
that
were
preserved
or
changed
after
traumatic
brain
injury.
Together,
findings
highlight
value
fibroblast
subsets
their
cellular
locations
toward
advancing
understanding
physiology
pathology.
Sensory
neurons
in
the
dorsal
root
ganglion
(DRG)
and
trigeminal
(TG)
are
specialized
to
detect
transduce
diverse
environmental
stimuli
central
nervous
system.
Single-cell
RNA
sequencing
has
provided
insights
into
diversity
of
sensory
ganglia
cell
types
rodents,
nonhuman
primates,
humans,
but
it
remains
difficult
compare
across
studies
species.
We
thus
constructed
harmonized
atlases
DRG
TG
that
describe
facilitate
comparison
18
neuronal
11
non-neuronal
six
species
31
datasets.
then
performed
single-cell/nucleus
from
both
human
highly
regenerative
axolotl
found
atlas
also
improves
type
annotation,
particularly
sparse
subtypes.
observed
transcriptomes
neuron
subtypes
broadly
similar
vertebrates,
expression
functionally
important
neuropeptides
channels
can
vary
notably.
The
resources
presented
here
guide
future
comparative
transcriptomics,
simplify
cell-type
nomenclature
differences
studies,
help
prioritize
targets
for
analgesic
development.
Cell,
Год журнала:
2024,
Номер
187(8), С. 1990 - 2009.e19
Опубликована: Март 20, 2024
Multiple
sclerosis
(MS)
is
a
neurological
disease
characterized
by
multifocal
lesions
and
smoldering
pathology.
Although
single-cell
analyses
provided
insights
into
cytopathology,
evolving
cellular
processes
underlying
MS
remain
poorly
understood.
We
investigated
the
dynamics
of
modeling
temporal
regional
rates
progression
in
mouse
experimental
autoimmune
encephalomyelitis
(EAE).
By
performing
spatial
expression
profiling
using
situ
sequencing
(ISS),
we
annotated
neighborhoods
found
centrifugal
evolution
active
lesions.
demonstrated
that
disease-associated
(DA)-glia
arise
independently
are
dynamically
induced
resolved
over
course.
Single-cell
mapping
human
archival
spinal
cords
confirmed
differential
distribution
homeostatic
DA-glia,
enabled
deconvolution
inactive
sub-compartments,
identified
new
lesion
areas.
establishing
resource
neuropathology
at
resolution,
our
study
unveils
intricate
MS.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Сен. 26, 2022
Abstract
After
spinal
cord
injury,
tissue
distal
to
the
lesion
contains
undamaged
cells
that
could
support
or
augment
recovery.
Targeting
these
requires
a
clearer
understanding
of
their
injury
responses
and
capacity
for
repair.
Here,
we
use
single
nucleus
RNA
sequencing
profile
how
each
cell
type
in
lumbar
changes
after
thoracic
mice.
We
present
an
atlas
dynamic
across
dozens
types
acute,
subacute,
chronically
injured
cord.
Using
this
resource,
find
rare
neurons
express
signature
regeneration
response
including
major
population
represent
spinocerebellar
projection
neurons.
characterize
anatomically
observed
axonal
sparing,
outgrowth,
remodeling
cerebellum.
Together,
work
provides
key
resource
studying
cellular
uncovers
spontaneous
plasticity
neurons,
uncovering
potential
candidate
targeted
therapy.
Chemical Reviews,
Год журнала:
2022,
Номер
122(18), С. 14842 - 14880
Опубликована: Сен. 7, 2022
The
widespread
adoption
of
microfluidic
devices
among
the
neuroscience
and
neurobiology
communities
has
enabled
addressing
a
broad
range
questions
at
molecular,
cellular,
circuit,
system
levels.
Here,
we
review
biomedical
engineering
approaches
that
harness
power
microfluidics
for
bottom-up
generation
neuronal
cell
types
assembly
analysis
neural
circuits.
Microfluidics-based
are
instrumental
to
generate
knowledge
necessary
derivation
diverse
from
human
pluripotent
stem
cells,
as
they
enable
isolation
subsequent
examination
individual
neurons
interest.
Moreover,
allow
engineer
circuits
with
specific
orientations
directionality
by
providing
control
over
polarity
permitting
axons
in
microchannels.
Similarly,
use
chips
enables
construction
not
only
2D
but
also
3D
brain,
retinal,
peripheral
nervous
model
Such
brain-on-a-chip
organoid-on-a-chip
technologies
promising
platforms
studying
these
organs
closely
recapitulate
some
aspects
vivo
biological
processes.
Microfluidic
models,
together
vitro
systems,
widely
used
many
applications
ranging
drug
development
toxicology
studies
neurological
disease
modeling
personalized
medicine.
Altogether,
provide
researchers
powerful
systems
complement
partially
replace
animal
models.
