Nature,
Год журнала:
2024,
Номер
635(8039), С. 679 - 689
Опубликована: Окт. 16, 2024
Human
prenatal
skin
is
populated
by
innate
immune
cells,
including
macrophages,
but
whether
they
act
solely
in
immunity
or
have
additional
functions
morphogenesis
unclear.
Here
we
assembled
a
comprehensive
multi-omics
reference
atlas
of
human
(7-17
post-conception
weeks),
combining
single-cell
and
spatial
transcriptomics
data,
to
characterize
the
microanatomical
tissue
niches
skin.
This
revealed
that
crosstalk
between
non-immune
cells
underpins
formation
hair
follicles,
implicated
scarless
wound
healing
crucial
for
angiogenesis.
We
systematically
compared
hair-bearing
organoid
(SkO)
model
derived
from
embryonic
stem
induced
pluripotent
adult
Cell,
Год журнала:
2023,
Номер
186(19), С. 4007 - 4037
Опубликована: Сен. 1, 2023
The
TGF-β
regulatory
system
plays
crucial
roles
in
the
preservation
of
organismal
integrity.
signaling
controls
metazoan
embryo
development,
tissue
homeostasis,
and
injury
repair
through
coordinated
effects
on
cell
proliferation,
phenotypic
plasticity,
migration,
metabolic
adaptation,
immune
surveillance
multiple
types
shared
ecosystems.
Defects
signaling,
particularly
epithelial
cells,
fibroblasts,
disrupt
tolerance,
promote
inflammation,
underlie
pathogenesis
fibrosis
cancer,
contribute
to
resistance
these
diseases
treatment.
Here,
we
review
how
coordinates
multicellular
response
programs
health
disease
this
knowledge
can
be
leveraged
develop
treatments
for
system.
Nano Letters,
Год журнала:
2021,
Номер
21(13), С. 5522 - 5531
Опубликована: Июнь 16, 2021
Cell-membrane-coated
nanoparticles
have
emerged
as
a
promising
antitumor
therapeutic
strategy.
However,
the
immunologic
mechanism
remains
elusive,
and
there
are
still
crucial
issues
to
be
addressed
including
tumor-homing
capacity,
immune
incompatibility,
immunogenicity.
Here,
we
reported
tumor-associated
macrophage
membrane
(TAMM)
derived
from
primary
tumor
with
unique
antigen-homing
affinity
capacity
compatibility.
TAMM
could
deplete
CSF1
secreted
by
cells
in
microenvironment
(TME),
blocking
interaction
between
TAM
cancer
cells.
Especially,
after
coating
upconversion
nanoparticle
conjugated
photosensitizer
(NPR@TAMM),
NPR@TAMM-mediated
photodynamic
immunotherapy
switched
activation
of
macrophages
an
immunosuppressive
M2-like
phenotype
more
inflammatory
M1-like
state,
induced
immunogenic
cell
death,
consequently
enhanced
immunity
efficiency
via
antigen-presenting
stimulate
production
tumor-specific
effector
T
metastatic
tumors.
This
TAM-membrane-based
approach
offers
new
strategy
for
personalized
therapy.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июль 26, 2023
Abstract
Ulcerative
colitis
and
Crohn’s
disease
are
chronic
inflammatory
intestinal
diseases
with
perplexing
heterogeneity
in
manifestation
response
to
treatment.
While
the
molecular
basis
for
this
remains
uncharacterized,
single-cell
technologies
allow
us
explore
transcriptional
states
within
tissues
at
an
unprecedented
resolution
which
could
further
understanding
of
these
complex
diseases.
Here,
we
apply
RNA-sequencing
human
inflamed
intestine
show
that
largest
differences
among
patients
present
myeloid
compartment
including
macrophages
neutrophils.
Using
spatial
transcriptomics
tissue
(CosMx
Spatial
Molecular
Imaging)
spatially
localize
each
macrophage
neutrophil
subsets
identified
by
unravel
diversity
based
on
their
localization.
Finally,
combined
analysis
reveals
a
strong
communication
network
involving
fibroblasts.
Our
data
sheds
light
cellular
complexity
points
towards
stromal
compartments
as
important
patient-to-patient
heterogeneity.
Cold Spring Harbor Perspectives in Biology,
Год журнала:
2022,
Номер
15(1), С. a041231 - a041231
Опубликована: Сен. 19, 2022
Myofibroblasts
are
the
construction
workers
of
wound
healing
and
repair
damaged
tissues
by
producing
organizing
collagen/extracellular
matrix
(ECM)
into
scar
tissue.
Scar
tissue
effectively
quickly
restores
mechanical
integrity
lost
architecture
but
comes
at
price
functionality.
Fibrotic
diseases
caused
excessive
or
persistent
myofibroblast
activity
can
lead
to
organ
failure.
This
review
defines
terminology,
phenotypic
characteristics,
functions.
We
will
focus
on
central
role
cell,
ECM,
mechanics
in
regulating
controlling
action.
Additionally,
we
discuss
how
therapies
based
intervention
potentially
ameliorate
outcomes.
Although
physiology
pathology
affect
all
organs,
emphasize
cutaneous
hypertrophic
scarring
as
paradigms
for
normal
versus
fibrosis.
A
message
this
is
that
myofibroblasts
be
activated
from
multiple
cell
sources,
varying
with
local
environment
type
injury,
either
restore
function
create
an
inappropriate
environment.
Cancer-associated
fibroblasts
(CAFs)
are
a
heterogeneous
cell
population
that
plays
crucial
role
in
remodeling
the
tumor
microenvironment
(TME).
Here,
through
integrated
analysis
of
spatial
and
single-cell
transcriptomics
data
across
six
common
cancer
types,
we
identified
four
distinct
functional
subgroups
CAFs
described
their
distribution
characteristics.
Additionally,
RNA
sequencing
(scRNA-seq)
from
three
additional
types
two
newly
generated
scRNA-seq
datasets
rare
namely
epithelial-myoepithelial
carcinoma
(EMC)
mucoepidermoid
(MEC),
expanded
our
understanding
CAF
heterogeneity.
Cell-cell
interaction
conducted
within
context
highlighted
pivotal
roles
matrix
(mCAFs)
angiogenesis
inflammatory
(iCAFs)
shaping
immunosuppressive
microenvironment.
In
patients
with
breast
(BRCA)
undergoing
anti-PD-1
immunotherapy,
iCAFs
demonstrated
heightened
capacity
facilitating
proliferation,
promoting
epithelial-mesenchymal
transition
(EMT),
contributing
to
establishment
an
Furthermore,
scoring
system
based
on
showed
significant
correlation
immune
therapy
response
melanoma
patients.
Lastly,
provided
web
interface
(
https://chenxisd.shinyapps.io/pancaf/
)
for
research
community
investigate
pan-cancer.
Compared
with
traditional
therapies,
targeted
therapy
has
merits
in
selectivity,
efficacy,
and
tolerability.
Small
molecule
inhibitors
are
one
of
the
primary
therapies
for
cancer.
Due
to
their
advantages
a
wide
range
targets,
convenient
medication,
ability
penetrate
into
central
nervous
system,
many
efforts
have
been
devoted
developing
more
small
inhibitors.
To
date,
88
approved
by
United
States
Food
Drug
Administration
treat
cancers.
Despite
remarkable
progress,
cancer
treatment
still
face
obstacles,
such
as
low
response
rate,
short
duration
response,
toxicity,
biomarkers,
resistance.
better
promote
development
targeting
cancers,
we
comprehensively
reviewed
involved
all
agents
pivotal
drug
candidates
clinical
trials
arranged
signaling
pathways
classification
We
discussed
lessons
learned
from
these
agents,
proper
strategies
overcome
resistance
arising
different
mechanisms,
combination
concerned
Through
our
review,
hoped
provide
insights
perspectives
research
treatment.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Сен. 19, 2023
Abstract
The
tumor
microenvironment
(TME)
is
comprised
of
non-malignant
cells
that
interact
with
each
other
and
cancer
cells,
critically
impacting
biology.
TME
complex,
understanding
it
requires
simplifying
approaches.
Here
we
provide
an
experimental-mathematical
approach
to
decompose
the
into
small
circuits
interacting
cell
types.
We
find,
using
female
breast
single-cell-RNA-sequencing
data,
a
hierarchical
network
interactions,
cancer-associated
fibroblasts
(CAFs)
at
top
secreting
factors
primarily
tumor-associated
macrophages
(TAMs).
This
composed
repeating
circuit
motifs.
isolate
strongest
two-cell
motif
by
culturing
in-vitro,
analyze
their
dynamics
transcriptomes.
isolated
recapitulates
hierarchy
in-vivo
enables
testing
effect
ligand-receptor
interactions
on
function,
as
demonstrate
identifying
mediator
CAF-TAM
-
RARRES2,
its
receptor
CMKLR1.
Thus,
complexity
may
be
simplified
circuits,
facilitating
development
strategies
modulate
TME.
