Sleep
loss
increases
AMPA-synaptic
strength
and
number
in
the
neocortex.
However,
this
is
only
part
of
synaptic
sleep
response.
We
report
an
increased
AMPA/NMDA
EPSC
ratio
frontal-cortical
pyramidal
neurons
layers
2–3.
Silent
synapses
are
absent,
decreasing
plastic
potential
to
convert
silent
NMDA
active
AMPA
synapses.
These
changes
recovered
by
sleep.
genes
enriched
for
shaping
cellular
components
controlling
glutamate
synapse
phenotype,
overlap
with
autism
risk
genes,
primarily
observed
excitatory
projecting
intra-telencephalically.
controlled
transcription
factor,
MEF2c,
its
repressor,
HDAC4.
can
thus
provide
a
framework
within
which
motor
learning
training
occur
mediated
sleep-dependent
oscillation
glutamate-synaptic
phenotypes.
Neuron,
Год журнала:
2024,
Номер
112(6), С. 924 - 941.e10
Опубликована: Янв. 17, 2024
The
properties
of
the
cell
types
that
are
selectively
vulnerable
in
Huntington's
disease
(HD)
cortex,
nature
somatic
CAG
expansions
mHTT
these
cells,
and
their
importance
CNS
circuitry
have
not
been
delineated.
Here,
we
employed
serial
fluorescence-activated
nuclear
sorting
(sFANS),
deep
molecular
profiling,
single-nucleus
RNA
sequencing
(snRNA-seq)
motor-cortex
samples
from
thirteen
predominantly
early
stage,
clinically
diagnosed
HD
donors
selected
cingulate,
visual,
insular,
prefrontal
cortices
to
demonstrate
loss
layer
5a
pyramidal
neurons
HD.
Extensive
occur
Betz
layers
6a
6b
resilient
Retrograde
tracing
experiments
macaque
brains
identify
as
corticostriatal
cells.
We
propose
enhanced
expansion
altered
synaptic
function
act
together
cause
disconnection
selective
neuronal
vulnerability
cerebral
cortex.
Women
live
longer
than
men
and
exhibit
less
cognitive
aging.
The
X
chromosome
contributes
to
sex
differences,
as
females
harbor
an
inactive
(Xi)
active
(Xa),
in
contrast
males
with
only
Xa.
Thus,
reactivation
of
silent
Xi
genes
may
contribute
differences.
We
use
allele-specific,
single-nucleus
RNA
sequencing
show
that
aging
remodels
transcription
the
Xa
across
hippocampal
cell
types.
Aging
preferentially
changed
gene
expression
on
X's
relative
autosomes.
Select
underwent
activation,
new
escape
cells
including
dentate
gyrus,
critical
learning
memory.
Expression
escapee
Plp1,
a
myelin
component,
was
increased
hippocampus
female
mice
parahippocampus
women.
AAV-mediated
Plp1
elevation
gyrus
male
improved
cognition.
Understanding
how
confer
advantage
could
lead
novel
targets
counter
brain
disease
both
sexes.
In
droplet-based
single-cell
and
single-nucleus
RNA-seq
experiments,
not
all
reads
associated
with
one
cell
barcode
originate
from
the
encapsulated
cell.
Such
background
noise
is
attributed
to
spillage
cell-free
ambient
RNA
or
swapping
events.
Abstract
Deconvolution
of
cell
mixtures
in
“bulk”
transcriptomic
samples
from
homogenate
human
tissue
is
important
for
understanding
disease
pathologies.
However,
several
experimental
and
computational
challenges
impede
transcriptomics-based
deconvolution
approaches
using
single-cell/nucleus
RNA-seq
reference
atlases.
Cells
the
brain
blood
have
substantially
different
sizes,
total
mRNA,
transcriptional
activities,
existing
may
quantify
mRNA
instead
type
proportions.
Further,
standards
are
lacking
use
atlases
integrative
analyses
single-cell
spatial
transcriptomics
data.
We
discuss
how
to
approach
these
key
with
orthogonal
“gold
standard”
datasets
evaluating
methods.
Trends in Plant Science,
Год журнала:
2024,
Номер
29(9), С. 1018 - 1028
Опубликована: Апрель 2, 2024
Plant
scientists
are
rapidly
integrating
single-cell
RNA
sequencing
(scRNA-seq)
into
their
workflows.
Maximizing
the
potential
of
scRNA-seq
requires
a
proper
understanding
spatiotemporal
context
cells.
However,
positional
information
is
inherently
lost
during
scRNA-seq,
limiting
its
to
characterize
complex
biological
systems.
In
this
review
we
highlight
how
current
analysis
pipelines
cannot
completely
recover
spatial
information,
which
confounds
interpretation.
Various
strategies
exist
identify
location
RNA,
from
classical
in
situ
hybridization
transcriptomics.
Herein
discuss
possibility
utilizing
supervise
analyses.
An
integrative
approach
will
maximize
each
technology,
and
lead
insights
go
beyond
capability
individual
technology.
Norepinephrine
(NE)
neurons
in
the
locus
coeruleus
(LC)
make
long-range
projections
throughout
central
nervous
system,
playing
critical
roles
arousal
and
mood,
as
well
various
components
of
cognition
including
attention,
learning,
memory.
The
LC-NE
system
is
also
implicated
multiple
neurological
neuropsychiatric
disorders.
Importantly,
are
highly
sensitive
to
degeneration
both
Alzheimer’s
Parkinson’s
disease.
Despite
clinical
importance
brain
region
prominent
role
a
variety
behavioral
functions,
detailed
molecular
characterization
LC
lacking.
Here,
we
used
combination
spatially-resolved
transcriptomics
single-nucleus
RNA-sequencing
characterize
landscape
transcriptomic
profile
human
brain.
We
provide
freely
accessible
resource
these
data
web-accessible
downloadable
formats.