Nature Immunology,
Год журнала:
2023,
Номер
24(5), С. 827 - 840
Опубликована: Март 16, 2023
Abstract
Resident
tissue
macrophages
(RTMs)
are
differentiated
immune
cells
that
populate
distinct
niches
and
exert
important
tissue-supportive
functions.
RTM
maintenance
is
thought
to
rely
either
on
differentiation
from
monocytes
or
self-renewal.
Here,
we
used
a
mouse
model
of
inducible
lung
interstitial
macrophage
(IM)
niche
depletion
refilling
investigate
the
development
IMs
in
vivo.
Using
time-course
single-cell
RNA-sequencing
analyses,
bone
marrow
chimeras
gene
targeting,
found
engrafted
Ly6C
+
classical
proliferated
locally
Csf1
receptor-dependent
manner
before
differentiating
into
IMs.
The
transition
monocyte
proliferation
toward
IM
subset
specification
was
controlled
by
transcription
factor
MafB,
while
c-Maf
specifically
regulated
identity
CD206
subset.
Our
data
provide
evidence
that,
mononuclear
phagocyte
system,
ability
proliferate
not
merely
restricted
myeloid
progenitor
mature
RTMs
but
also
tightly
capability
developing
Cancer Cell,
Год журнала:
2021,
Номер
39(5), С. 649 - 661.e5
Опубликована: Март 12, 2021
Immune
checkpoint
blockade
(ICB)
results
in
durable
disease
control
a
subset
of
patients
with
advanced
renal
cell
carcinoma
(RCC),
but
mechanisms
driving
resistance
are
poorly
understood.
We
characterize
the
single-cell
transcriptomes
cancer
and
immune
cells
from
metastatic
RCC
before
or
after
ICB
exposure.
In
responders,
subsets
cytotoxic
T
express
higher
levels
co-inhibitory
receptors
effector
molecules.
Macrophages
treated
biopsies
shift
toward
pro-inflammatory
states
response
to
an
interferon-rich
microenvironment
also
upregulate
immunosuppressive
markers.
cells,
we
identify
bifurcation
into
two
subpopulations
differing
angiogenic
signaling
upregulation
programs
ICB.
Expression
signatures
for
evasion
associated
PBRM1
mutation
survival
primary
ICB-treated
RCC.
Our
findings
demonstrate
that
remodels
modifies
interplay
between
populations
critical
understanding
Cancer Discovery,
Год журнала:
2021,
Номер
12(1), С. 134 - 153
Опубликована: Авг. 20, 2021
Abstract
Liver
metastasis,
the
leading
cause
of
colorectal
cancer
mortality,
exhibits
a
highly
heterogeneous
and
suppressive
immune
microenvironment.
Here,
we
sequenced
97
matched
samples
by
using
single-cell
RNA
sequencing
spatial
transcriptomics.
Strikingly,
metastatic
microenvironment
underwent
remarkable
reprogramming
immunosuppressive
cells
such
as
MRC1+
CCL18+
M2-like
macrophages.
We
further
developed
scMetabolism,
computational
pipeline
for
quantifying
metabolism,
observed
that
those
macrophages
harbored
enhanced
metabolic
activity.
Interestingly,
neoadjuvant
chemotherapy
could
block
this
status
restore
antitumor
balance
in
responsive
patients,
whereas
nonresponsive
patients
deteriorated
into
more
one.
Our
work
described
evolution
metastasis
uncovered
black
box
how
tumors
respond
to
chemotherapy.
Significance:
present
atlas
liver
found
metabolically
activated
sites.
Efficient
can
slow
down
activation,
raising
possibility
target
metabolism
pathways
metastasis.
This
article
is
highlighted
In
Issue
feature,
p.
1
Molecular Systems Biology,
Год журнала:
2021,
Номер
17(1)
Опубликована: Янв. 1, 2021
As
the
number
of
single-cell
transcriptomics
datasets
grows,
natural
next
step
is
to
integrate
accumulating
data
achieve
a
common
ontology
cell
types
and
states.
However,
it
not
straightforward
compare
gene
expression
levels
across
automatically
assign
type
labels
in
new
dataset
based
on
existing
annotations.
In
this
manuscript,
we
demonstrate
that
our
previously
developed
method,
scVI,
provides
an
effective
fully
probabilistic
approach
for
joint
representation
analysis
scRNA-seq
data,
while
accounting
uncertainty
caused
by
biological
measurement
noise.
We
also
introduce
ANnotation
using
Variational
Inference
(scANVI),
semi-supervised
variant
scVI
designed
leverage
state
scANVI
favorably
state-of-the-art
methods
integration
annotation
terms
accuracy,
scalability,
adaptability
challenging
settings.
contrast
methods,
multiple
with
single
generative
model
can
be
directly
used
downstream
tasks,
such
as
differential
expression.
Both
are
easily
accessible
through
scvi-tools.
Nucleic Acids Research,
Год журнала:
2020,
Номер
48(W1), С. W177 - W184
Опубликована: Март 24, 2020
The
Galaxy
HiCExplorer
provides
a
web
service
at
https://hicexplorer.usegalaxy.eu.
It
enables
the
integrative
analysis
of
chromosome
conformation
by
providing
tools
and
computational
resources
to
pre-process,
analyse
visualize
Hi-C,
Capture
Hi-C
(cHi-C)
single-cell
(scHi-C)
data.
Since
last
publication,
has
been
expanded
considerably
with
new
facilitate
cHi-C
provide
an
in-depth
Moreover,
it
supports
scHi-C
data
offering
broad
range
tools.
With
help
standard
graphical
user
interface
Galaxy,
presented
workflows,
extensive
documentation
tutorials,
novices
as
well
experts
are
supported
in
their
HiCExplorer.
Following
cancer
through
the
body
The
heterogeneity
of
mammalian
tumors
has
been
well
documented,
but
it
remains
unknown
how
differences
between
individual
cells
lead
to
metastasis
and
spread
throughout
body.
Quinn
et
al.
created
a
Cas9-based
lineage
tracer
used
single-cell
sequencing
generate
phylogenies
follow
movement
metastatic
human
implanted
in
lung
mouse
xenograph
model.
Using
this
model,
they
found
that
within
same
cell
line,
exhibited
diverse
phenotypes.
These
subclones
differential
gene
expression
profiles,
some
which
were
previously
associated
with
metastasis.
Science
,
issue
p.
eabc1944
Cell,
Год журнала:
2022,
Номер
185(11), С. 1905 - 1923.e25
Опубликована: Май 1, 2022
Tumor
evolution
is
driven
by
the
progressive
acquisition
of
genetic
and
epigenetic
alterations
that
enable
uncontrolled
growth
expansion
to
neighboring
distal
tissues.
The
study
phylogenetic
relationships
between
cancer
cells
provides
key
insights
into
these
processes.
Here,
we
introduced
an
evolving
lineage-tracing
system
with
a
single-cell
RNA-seq
readout
mouse
model
Kras;Trp53(KP)-driven
lung
adenocarcinoma
tracked
tumor
from
single-transformed
metastatic
tumors
at
unprecedented
resolution.
We
found
loss
initial,
stable
alveolar-type2-like
state
was
accompanied
transient
increase
in
plasticity.
This
followed
adoption
distinct
transcriptional
programs
rapid
and,
ultimately,
clonal
sweep
subclones
capable
metastasizing.
Finally,
develop
through
stereotypical
evolutionary
trajectories,
perturbing
additional
suppressors
accelerates
progression
creating
novel
trajectories.
Our
elucidates
hierarchical
nature
more
broadly,
enables
in-depth
studies
progression.
