Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Nov. 4, 2022
Abstract
Cancer-associated
fibroblasts
(CAFs)
are
the
predominant
components
of
tumor
microenvironment
(TME)
and
influence
cancer
hallmarks,
but
without
systematic
investigation
on
their
ubiquitous
characteristics
across
different
types.
Here,
we
perform
pan-cancer
analysis
226
samples
10
solid
types
to
profile
TME
at
single-cell
resolution,
illustrating
commonalities/plasticity
heterogenous
CAFs.
Activation
trajectory
major
CAF
is
divided
into
three
states,
exhibiting
distinct
interactions
with
other
cell
components,
relating
prognosis
immunotherapy.
Moreover,
minor
represent
alternative
origin
from
(e.g.,
endothelia
macrophages).
Particularly,
presentation
endothelial-to-mesenchymal
transition
CAF,
which
may
interact
proximal
SPP
1
+
tumor-associated
macrophages,
implicated
in
survival
stratifications.
Our
study
comprehensively
profiles
shared
dynamics
CAFs,
highlight
heterogeneity
plasticity
Browser
integrated
information
available
https://gist-fgl.github.io/sc-caf-atlas/
.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: Feb. 17, 2021
Understanding
global
communications
among
cells
requires
accurate
representation
of
cell-cell
signaling
links
and
effective
systems-level
analyses
those
links.
We
construct
a
database
interactions
ligands,
receptors
their
cofactors
that
accurately
represent
known
heteromeric
molecular
complexes.
then
develop
CellChat,
tool
is
able
to
quantitatively
infer
analyze
intercellular
communication
networks
from
single-cell
RNA-sequencing
(scRNA-seq)
data.
CellChat
predicts
major
inputs
outputs
for
how
signals
coordinate
functions
using
network
analysis
pattern
recognition
approaches.
Through
manifold
learning
quantitative
contrasts,
classifies
pathways
delineates
conserved
context-specific
across
different
datasets.
Applying
mouse
human
skin
datasets
shows
its
ability
extract
complex
patterns.
Our
versatile
easy-to-use
toolkit
web-based
Explorer
(
http://www.cellchat.org/
)
will
help
discover
novel
build
atlases
in
diverse
tissues.
Cell,
Journal Year:
2021,
Volume and Issue:
184(3), P. 792 - 809.e23
Published: Feb. 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.
Science,
Journal Year:
2021,
Volume and Issue:
374(6574)
Published: Dec. 16, 2021
T
cells
play
a
central
role
in
cancer
immunotherapy,
but
we
lack
systematic
comparison
of
the
heterogeneity
and
dynamics
tumor-infiltrating
across
types.
We
built
single-cell
RNA-sequencing
pan-cancer
atlas
for
316
donors
21
types
revealed
distinct
cell
composition
patterns.
found
multiple
state-transition
paths
exhaustion
CD8+
preference
those
among
different
tumor
Certain
populations
showed
specific
correlation
with
patient
properties
such
as
mutation
burden,
shedding
light
on
possible
determinants
microenvironment.
compositions
within
tumors
alone
could
classify
patients
into
groups
clinical
trait
specificity,
providing
new
insights
immunity
precision
immunotherapy
targeting
cells.
Cell,
Journal Year:
2020,
Volume and Issue:
182(2), P. 497 - 514.e22
Published: June 23, 2020
To
define
the
cellular
composition
and
architecture
of
cutaneous
squamous
cell
carcinoma
(cSCC),
we
combined
single-cell
RNA
sequencing
with
spatial
transcriptomics
multiplexed
ion
beam
imaging
from
a
series
human
cSCCs
matched
normal
skin.
cSCC
exhibited
four
tumor
subpopulations,
three
recapitulating
epidermal
states,
tumor-specific
keratinocyte
(TSK)
population
unique
to
cancer,
which
localized
fibrovascular
niche.
Integration
data
mapped
ligand-receptor
networks
specific
types,
revealing
TSK
cells
as
hub
for
intercellular
communication.
Multiple
features
potential
immunosuppression
were
observed,
including
T
regulatory
(Treg)
co-localization
CD8
in
compartmentalized
stroma.
Finally,
characterization
xenografts
vivo
CRISPR
screens
identified
essential
roles
subpopulation-enriched
gene
tumorigenesis.
These
stromal
niches
where
they
interact,
communicating
that
engage
cancer.
Cell,
Journal Year:
2022,
Volume and Issue:
185(2), P. 379 - 396.e38
Published: Jan. 1, 2022
The
liver
is
the
largest
solid
organ
in
body,
yet
it
remains
incompletely
characterized.
Here
we
present
a
spatial
proteogenomic
atlas
of
healthy
and
obese
human
murine
combining
single-cell
CITE-seq,
single-nuclei
sequencing,
transcriptomics,
proteomics.
By
integrating
these
multi-omic
datasets,
provide
validated
strategies
to
reliably
discriminate
localize
all
hepatic
cells,
including
population
lipid-associated
macrophages
(LAMs)
at
bile
ducts.
We
then
align
this
across
seven
species,
revealing
conserved
program
bona
fide
Kupffer
cells
LAMs.
also
uncover
respective
spatially
resolved
cellular
niches
microenvironmental
circuits
driving
their
unique
transcriptomic
identities.
demonstrate
that
LAMs
are
induced
by
local
lipid
exposure,
leading
induction
steatotic
regions
liver,
while
cell
development
crucially
depends
on
cross-talk
with
stellate
via
evolutionarily
ALK1-BMP9/10
axis.
