Nature,
Год журнала:
2023,
Номер
617(7961), С. 599 - 607
Опубликована: Май 3, 2023
Abstract
Gliomas
synaptically
integrate
into
neural
circuits
1,2
.
Previous
research
has
demonstrated
bidirectional
interactions
between
neurons
and
glioma
cells,
with
neuronal
activity
driving
growth
1–4
gliomas
increasing
excitability
2,5–8
Here
we
sought
to
determine
how
glioma-induced
changes
influence
underlying
cognition
whether
these
patient
survival.
Using
intracranial
brain
recordings
during
lexical
retrieval
language
tasks
in
awake
humans
together
site-specific
tumour
tissue
biopsies
cell
biology
experiments,
find
that
remodel
functional
circuitry
such
task-relevant
responses
activate
tumour-infiltrated
cortex
well
beyond
the
cortical
regions
are
normally
recruited
healthy
brain.
Site-directed
from
within
exhibit
high
connectivity
rest
of
enriched
for
a
glioblastoma
subpopulation
exhibits
distinct
synaptogenic
neuronotrophic
phenotype.
Tumour
cells
functionally
connected
secrete
factor
thrombospondin-1,
which
contributes
differential
neuron–glioma
observed
compared
less
connectivity.
Pharmacological
inhibition
thrombospondin-1
using
FDA-approved
drug
gabapentin
decreases
proliferation.
The
degree
normal
negatively
affects
both
survival
performance
tasks.
These
data
demonstrate
high-grade
human
brain,
promotes
progression
impairs
cognition.
The
SARS-CoV-2
pandemic
affecting
the
human
respiratory
system
severely
challenges
public
health
and
urgently
demands
for
increasing
our
understanding
of
COVID-19
pathogenesis,
especially
host
factors
facilitating
virus
infection
replication.
was
reported
to
enter
cells
via
binding
ACE2,
followed
by
its
priming
TMPRSS2.
Here,
we
investigate
ACE2
TMPRSS2
expression
levels
their
distribution
across
cell
types
in
lung
tissue
(twelve
donors,
39,778
cells)
derived
from
subsegmental
bronchial
branches
(four
17,521
single
nuclei
RNA
sequencing,
respectively.
While
is
strongly
expressed
both
tissues,
predominantly
a
transient
secretory
type.
Interestingly,
these
transiently
differentiating
show
an
enrichment
pathways
related
RHO
GTPase
function
viral
processes
suggesting
increased
vulnerability
infection.
Our
data
provide
rich
resource
future
investigations
pathogenesis.
Nature,
Год журнала:
2021,
Номер
598(7879), С. 111 - 119
Опубликована: Окт. 6, 2021
Abstract
The
primary
motor
cortex
(M1)
is
essential
for
voluntary
fine-motor
control
and
functionally
conserved
across
mammals
1
.
Here,
using
high-throughput
transcriptomic
epigenomic
profiling
of
more
than
450,000
single
nuclei
in
humans,
marmoset
monkeys
mice,
we
demonstrate
a
broadly
cellular
makeup
this
region,
with
similarities
that
mirror
evolutionary
distance
are
consistent
between
the
transcriptome
epigenome.
core
molecular
identities
neuronal
non-neuronal
cell
types
allow
us
to
generate
cross-species
consensus
classification
types,
infer
properties
species.
Despite
overall
conservation,
however,
many
species-dependent
specializations
apparent,
including
differences
cell-type
proportions,
gene
expression,
DNA
methylation
chromatin
state.
Few
marker
genes
species,
revealing
short
list
candidate
regulatory
mechanisms
responsible
features
homologous
such
as
GABAergic
chandelier
cells.
This
allows
use
patch–seq
(a
combination
whole-cell
patch-clamp
recordings,
RNA
sequencing
morphological
characterization)
identify
corticospinal
Betz
cells
from
layer
5
non-human
primates
characterize
their
highly
specialized
physiology
anatomy.
These
findings
highlight
robust
underpinnings
diversity
M1
mammals,
point
pathways
functional
identity
species-specific
adaptations.
Nature Medicine,
Год журнала:
2020,
Номер
26(5), С. 792 - 802
Опубликована: Май 1, 2020
Abstract
Single-cell
genomics
is
essential
to
chart
tumor
ecosystems.
Although
single-cell
RNA-Seq
(scRNA-Seq)
profiles
RNA
from
cells
dissociated
fresh
tumors,
single-nucleus
(snRNA-Seq)
needed
profile
frozen
or
hard-to-dissociate
tumors.
Each
requires
customization
different
tissue
and
types,
posing
a
barrier
adoption.
Here,
we
have
developed
systematic
toolbox
for
profiling
clinical
samples
using
scRNA-Seq
snRNA-Seq,
respectively.
We
analyzed
216,490
nuclei
40
across
23
specimens
spanning
eight
types
of
varying
sample
characteristics.
evaluated
protocols
by
cell
nucleus
quality,
recovery
rate
cellular
composition.
snRNA-Seq
matched
recovered
the
same
but
at
proportions.
Our
work
provides
guidance
studies
in
broad
range
including
criteria
testing
selecting
methods
other
thus
paving
way
charting
atlases.
Abstract
Background
Single-cell
RNA
sequencing
has
been
widely
adopted
to
estimate
the
cellular
composition
of
heterogeneous
tissues
and
obtain
transcriptional
profiles
individual
cells.
Multiple
approaches
for
optimal
sample
dissociation
storage
single
cells
have
proposed
as
single-nuclei
profiling
methods.
What
lacking
is
a
systematic
comparison
their
relative
biases
benefits.
Results
Here,
we
compare
gene
expression
single-cell
suspensions
prepared
from
adult
mouse
kidney
using
two
tissue
protocols.
For
each
sample,
also
fresh
cryopreserved
methanol-fixed
Lastly,
this
data
that
generated
three
single-nucleus
workflows.
Our
confirms
prior
reports
digestion
on
ice
avoids
stress
response
observed
with
37
°C
dissociation.
It
reveals
cell
types
more
abundant
either
in
cold
or
warm
dissociations
may
represent
populations
require
gentler
harsher
conditions
be
released
intact.
storage,
cryopreservation
dissociated
results
major
loss
epithelial
types;
contrast,
methanol
fixation
maintains
but
suffers
ambient
leakage.
Finally,
type
differences
are
between
libraries.
In
particular,
note
an
underrepresentation
T,
B,
NK
lymphocytes
Conclusions
Systematic
recovered
across
workflows
highlighted
protocol-specific
thus
enables
researchers
starting
experiments
make
informed
choice.
Journal of Hematology & Oncology,
Год журнала:
2020,
Номер
13(1)
Опубликована: Дек. 1, 2020
Abstract
Over
the
past
few
decades,
RNA
sequencing
has
significantly
progressed,
becoming
a
paramount
approach
for
transcriptome
profiling.
The
revolution
from
bulk
to
single-molecular,
single-cell
and
spatial
approaches
enabled
increasingly
accurate,
individual
cell
resolution
incorporated
with
information.
Cancer,
major
malignant
heterogeneous
lethal
disease,
remains
an
enormous
challenge
in
medical
research
clinical
treatment.
As
vital
tool,
been
utilized
many
aspects
of
cancer
therapy,
including
biomarker
discovery
characterization
heterogeneity
evolution,
drug
resistance,
immune
microenvironment
immunotherapy,
neoantigens
so
on.
In
this
review,
latest
studies
on
technology
their
applications
are
summarized,
future
challenges
opportunities
discussed.
