Nature,
Год журнала:
2021,
Номер
598(7879), С. 129 - 136
Опубликована: Окт. 6, 2021
Abstract
The
mammalian
cerebrum
performs
high-level
sensory
perception,
motor
control
and
cognitive
functions
through
highly
specialized
cortical
subcortical
structures
1
.
Recent
surveys
of
mouse
human
brains
with
single-cell
transcriptomics
2–6
high-throughput
imaging
technologies
7,8
have
uncovered
hundreds
neural
cell
types
distributed
in
different
brain
regions,
but
the
transcriptional
regulatory
programs
that
are
responsible
for
unique
identity
function
each
type
remain
unknown.
Here
we
probe
accessible
chromatin
more
than
800,000
individual
nuclei
from
45
regions
span
adult
isocortex,
olfactory
bulb,
hippocampus
cerebral
nuclei,
use
resulting
data
to
map
state
491,818
candidate
cis
-regulatory
DNA
elements
160
distinct
types.
We
find
high
specificity
spatial
distribution
not
only
excitatory
neurons,
also
most
classes
inhibitory
neurons
a
subset
glial
characterize
gene
sequences
associated
regional
within
these
further
link
considerable
fraction
putative
target
genes
expressed
diverse
predict
regulators
involved
broad
spectrum
molecular
cellular
pathways
neuronal
populations.
Our
results
provide
foundation
comprehensive
analysis
assist
interpretation
noncoding
risk
variants
various
neurological
diseases
traits
humans.
European Journal of Immunology,
Год журнала:
2019,
Номер
49(10), С. 1457 - 1973
Опубликована: Окт. 1, 2019
These
guidelines
are
a
consensus
work
of
considerable
number
members
the
immunology
and
flow
cytometry
community.
They
provide
theory
key
practical
aspects
enabling
immunologists
to
avoid
common
errors
that
often
undermine
immunological
data.
Notably,
there
comprehensive
sections
all
major
immune
cell
types
with
helpful
Tables
detailing
phenotypes
in
murine
human
cells.
The
latest
techniques
applications
also
described,
featuring
examples
data
can
be
generated
and,
importantly,
how
analysed.
Furthermore,
tips,
tricks
pitfalls
avoid,
written
peer-reviewed
by
leading
experts
field,
making
this
an
essential
research
companion.
Mapping
the
mammalian
brain
The
diverse
physiology
of
is
reflected
in
its
complex
organization
at
regional,
cellular,
and
subcellular
levels.
Sjöstedt
et
al.
combined
data—both
newly
acquired
from
other
large-scale
mapping
projects—from
transcriptomics,
single-cell
genomics,
situ
hybridization,
antibody-based
protein
profiling
to
map
molecular
profiles
human,
pig,
mouse
brain.
analysis
consistent
with
a
conserved
basic
architecture
during
evolution,
but
it
does
show
differences
regional
gene
expression
profiles.
Science
,
this
issue
p.
eaay5947
PLoS ONE,
Год журнала:
2018,
Номер
13(12), С. e0209648 - e0209648
Опубликована: Дек. 26, 2018
Transcriptomic
profiling
of
complex
tissues
by
single-nucleus
RNA-sequencing
(snRNA-seq)
affords
some
advantages
over
single-cell
(scRNA-seq).
snRNA-seq
provides
less
biased
cellular
coverage,
does
not
appear
to
suffer
cell
isolation-based
transcriptional
artifacts,
and
can
be
applied
archived
frozen
specimens.
We
used
well-matched
scRNA-seq
datasets
from
mouse
visual
cortex
compare
type
detection.
Although
more
transcripts
are
detected
in
individual
whole
cells
(~11,000
genes)
than
nuclei
(~7,000
genes),
we
demonstrate
that
closely
related
neuronal
types
similarly
discriminated
with
both
methods
if
intronic
sequences
included
analysis.
estimate
the
nuclear
proportion
total
mRNA
varies
20%
50%
for
large
small
pyramidal
neurons,
respectively.
Together,
these
results
illustrate
high
information
content
RNA
characterization
diversity
brain
tissues.
Abstract
Single-cell
transcriptomics
(scRNA-seq)
has
become
essential
for
biomedical
research
over
the
past
decade,
particularly
in
developmental
biology,
cancer,
immunology,
and
neuroscience.
Most
commercially
available
scRNA-seq
protocols
require
cells
to
be
recovered
intact
viable
from
tissue.
This
precluded
many
cell
types
study
largely
destroys
spatial
context
that
could
otherwise
inform
analyses
of
identity
function.
An
increasing
number
platforms
now
facilitate
spatially
resolved,
high-dimensional
assessment
gene
transcription,
known
as
‘spatial
transcriptomics’.
Here,
we
introduce
different
classes
method,
which
either
record
locations
hybridized
mRNA
molecules
tissue,
image
positions
themselves
prior
assessment,
or
employ
arrays
probes
pre-determined
location.
We
review
sizes
tissue
area
can
assessed,
their
resolution,
genes
profiled.
discuss
if
preservation
influences
choice
platform,
provide
guidance
on
whether
specific
may
better
suited
discovery
screens
hypothesis
testing.
Finally,
bioinformatic
methods
analysing
transcriptomic
data,
including
pre-processing,
integration
with
existing
inference
cell-cell
interactions.
Spatial
-omics
are
already
improving
our
understanding
human
tissues
research,
diagnostic,
therapeutic
settings.
To
build
upon
these
recent
advancements,
entry-level
those
seeking
own
research.
Nature,
Год журнала:
2021,
Номер
598(7879), С. 86 - 102
Опубликована: Окт. 6, 2021
Here
we
report
the
generation
of
a
multimodal
cell
census
and
atlas
mammalian
primary
motor
cortex
as
initial
product
BRAIN
Initiative
Cell
Census
Network
(BICCN).
This
was
achieved
by
coordinated
large-scale
analyses
single-cell
transcriptomes,
chromatin
accessibility,
DNA
methylomes,
spatially
resolved
morphological
electrophysiological
properties
cellular
resolution
input-output
mapping,
integrated
through
cross-modal
computational
analysis.
Our
results
advance
collective
knowledge
understanding
brain
cell-type
organization
Cell,
Год журнала:
2020,
Номер
181(2), С. 236 - 249
Опубликована: Апрель 1, 2020
Crucial
transitions
in
cancer-including
tumor
initiation,
local
expansion,
metastasis,
and
therapeutic
resistance-involve
complex
interactions
between
cells
within
the
dynamic
ecosystem.
Transformative
single-cell
genomics
technologies
spatial
multiplex
situ
methods
now
provide
an
opportunity
to
interrogate
this
complexity
at
unprecedented
resolution.
The
Human
Tumor
Atlas
Network
(HTAN),
part
of
National
Cancer
Institute
(NCI)
Moonshot
Initiative,
will
establish
a
clinical,
experimental,
computational,
organizational
framework
generate
informative
accessible
three-dimensional
atlases
cancer
for
diverse
set
types.
This
effort
complements
both
ongoing
efforts
map
healthy
organs
previous
large-scale
approaches
focused
on
bulk
sequencing
single
point
time.
Generating
single-cell,
multiparametric,
longitudinal
integrating
them
with
clinical
outcomes
should
help
identify
novel
predictive
biomarkers
features
as
well
therapeutically
relevant
cell
types,
states,
cellular
across
transitions.
resulting
have
profound
impact
our
understanding
biology
potential
improve
detection,
prevention,
discovery
better
precision-medicine
treatments
patients
those
risk
cancer.
Nature,
Год журнала:
2023,
Номер
624(7991), С. 317 - 332
Опубликована: Дек. 13, 2023
The
mammalian
brain
consists
of
millions
to
billions
cells
that
are
organized
into
many
cell
types
with
specific
spatial
distribution
patterns
and
structural
functional
properties1-3.
Here
we
report
a
comprehensive
high-resolution
transcriptomic
cell-type
atlas
for
the
whole
adult
mouse
brain.
was
created
by
combining
single-cell
RNA-sequencing
(scRNA-seq)
dataset
around
7
million
profiled
(approximately
4.0
passing
quality
control),
approximately
4.3
using
multiplexed
error-robust
fluorescence
in
situ
hybridization
(MERFISH).
is
hierarchically
4
nested
levels
classification:
34
classes,
338
subclasses,
1,201
supertypes
5,322
clusters.
We
present
an
online
platform,
Allen
Brain
Cell
Atlas,
visualize
whole-brain
along
MERFISH
datasets.
systematically
analysed
neuronal
non-neuronal
across
identified
high
degree
correspondence
between
identity
specificity
each
type.
results
reveal
unique
features
organization
different
regions-in
particular,
dichotomy
dorsal
ventral
parts
part
contains
relatively
fewer
yet
highly
divergent
types,
whereas
more
numerous
closely
related
other.
Our
study
also
uncovered
extraordinary
diversity
heterogeneity
neurotransmitter
neuropeptide
expression
co-expression
types.
Finally,
found
transcription
factors
major
determinants
classification
combinatorial
factor
code
defines
all
establishes
benchmark
reference
foundational
resource
integrative
investigations
cellular
circuit
function,
development
evolution