Abstract
Background
As
core
units
of
organ
tissues,
cells
various
types
play
their
harmonious
rhythms
to
maintain
the
homeostasis
human
body.
It
is
essential
identify
characteristics
in
organs
and
regulatory
networks
for
understanding
biological
mechanisms
related
health
disease.
However,
a
systematic
comprehensive
single-cell
transcriptional
profile
across
multiple
normal
adult
missing.
Results
We
perform
transcriptomes
84,363
derived
from
15
tissue
one
donor
generate
an
cell
atlas.
The
atlas
depicts
252
subtypes
cells,
including
major
such
as
T,
B,
myeloid,
epithelial,
stromal
well
novel
COCH
+
fibroblasts
FibSmo
each
which
distinguished
by
marker
genes
profiles.
These
collectively
contribute
heterogeneity
organs.
Moreover,
T
B
receptor
repertoire
comparisons
trajectory
analyses
reveal
direct
clonal
sharing
with
developmental
states
among
different
tissues.
Furthermore,
markers,
transcription
factors,
ligand-receptor
pairs
are
identified
potential
functional
regulations
maintaining
Conclusions
reveals
inter-
intra-organ
provides
useful
resource
uncovering
key
events
during
development
diseases
context
Science,
Год журнала:
2020,
Номер
370(6518), С. 856 - 860
Опубликована: Окт. 20, 2020
The
causative
agent
of
coronavirus
disease
2019
(COVID-19)
is
the
severe
acute
respiratory
syndrome
2
(SARS-CoV-2).
For
many
viruses,
tissue
tropism
determined
by
availability
virus
receptors
and
entry
cofactors
on
surface
host
cells.
In
this
study,
we
found
that
neuropilin-1
(NRP1),
known
to
bind
furin-cleaved
substrates,
significantly
potentiates
SARS-CoV-2
infectivity,
an
effect
blocked
a
monoclonal
blocking
antibody
against
NRP1.
A
mutant
with
altered
furin
cleavage
site
did
not
depend
NRP1
for
infectivity.
Pathological
analysis
olfactory
epithelium
obtained
from
human
COVID-19
autopsies
revealed
infected
NRP1-positive
cells
facing
nasal
cavity.
Our
data
provide
insight
into
cell
infectivity
define
potential
target
antiviral
intervention.
Cell,
Год журнала:
2021,
Номер
184(3), С. 792 - 809.e23
Опубликована: Фев. 1, 2021
Tumor-infiltrating
myeloid
cells
(TIMs)
are
key
regulators
in
tumor
progression,
but
the
similarity
and
distinction
of
their
fundamental
properties
across
different
tumors
remain
elusive.
Here,
by
performing
a
pan-cancer
analysis
single
from
210
patients
15
human
cancer
types,
we
identified
distinct
features
TIMs
types.
Mast
nasopharyngeal
were
found
to
be
associated
with
better
prognosis
exhibited
an
anti-tumor
phenotype
high
ratio
TNF+/VEGFA+
cells.
Systematic
comparison
between
cDC1-
cDC2-derived
LAMP3+
cDCs
revealed
differences
transcription
factors
external
stimulus.
Additionally,
pro-angiogenic
tumor-associated
macrophages
(TAMs)
characterized
diverse
markers
composition
appeared
certain
somatic
mutations
gene
expressions.
Our
results
provide
systematic
view
highly
heterogeneous
suggest
future
avenues
for
rational,
targeted
immunotherapies.
Molecular
characterization
of
cell
types
using
single-cell
transcriptome
sequencing
is
revolutionizing
biology
and
enabling
new
insights
into
the
physiology
human
organs.
We
created
a
reference
atlas
comprising
nearly
500,000
cells
from
24
different
tissues
organs,
many
same
donor.
This
enabled
molecular
more
than
400
types,
their
distribution
across
tissues,
tissue-specific
variation
in
gene
expression.
Using
multiple
single
donor
identification
clonal
T
between
mutation
rate
B
cells,
analysis
cycle
state
proliferative
potential
shared
tissues.
Cell
type–specific
RNA
splicing
was
discovered
analyzed
within
an
individual.
Despite
their
crucial
role
in
health
and
disease,
our
knowledge
of
immune
cells
within
human
tissues
remains
limited.
We
surveyed
the
compartment
16
from
12
adult
donors
by
single-cell
RNA
sequencing
VDJ
generating
a
dataset
~360,000
cells.
To
systematically
resolve
cell
heterogeneity
across
tissues,
we
developed
CellTypist,
machine
learning
tool
for
rapid
precise
type
annotation.
Using
this
approach,
combined
with
detailed
curation,
determined
tissue
distribution
finely
phenotyped
types,
revealing
hitherto
unappreciated
tissue-specific
features
clonal
architecture
T
B
Our
multitissue
approach
lays
foundation
identifying
highly
resolved
types
leveraging
common
reference
dataset,
tissue-integrated
expression
analysis,
antigen
receptor
sequencing.
Computational and Structural Biotechnology Journal,
Год журнала:
2021,
Номер
19, С. 3796 - 3798
Опубликована: Янв. 1, 2021
UCell
is
an
R
package
for
evaluating
gene
signatures
in
single-cell
datasets.
signature
scores,
based
on
the
Mann-Whitney
U
statistic,
are
robust
to
dataset
size
and
heterogeneity,
their
calculation
demands
less
computing
time
memory
than
other
available
methods,
enabling
processing
of
large
datasets
a
few
minutes
even
machines
with
limited
power.
can
be
applied
any
data
matrix,
includes
functions
directly
interact
Seurat
objects.
The
documentation
GitHub
at
https://github.com/carmonalab/UCell.