Although
the
age
of
genome
gave
us
much
insight
about
how
our
organs
fail
with
disease,
it
also
suggested
that
diseases
do
not
arise
from
mutations
alone;
rather,
they
develop
as
we
age.
In
this
Review,
examine
wound
healing
might
act
to
ignite
disease.
Wound
works
well
when
are
younger,
repairing
damage
accidents,
environmental
assaults,
and
battles
pathogens.
Yet,
accumulation
tissue
damage,
repair
process
can
devolve,
leading
inflammation,
fibrosis,
neoplastic
signaling.
We
discuss
healthy
responses
bodies
misappropriate
these
pathways
in
focus
predominantly
on
epithelial-based
(lung
skin)
diseases,
similar
operate
cardiac,
muscle,
neuronal
diseases.
The
response
to
tumor-initiating
inflammatory
and
genetic
insults
can
vary
among
morphologically
indistinguishable
cells,
suggesting
as
yet
uncharacterized
roles
for
epigenetic
plasticity
during
early
neoplasia.
To
investigate
the
origins
impact
of
such
plasticity,
we
performed
single-cell
analyses
on
normal,
inflamed,
premalignant,
malignant
tissues
in
autochthonous
models
pancreatic
cancer.
We
reproducibly
identified
heterogeneous
cell
states
that
are
primed
diverse,
late-emerging
neoplastic
fates
linked
these
chromatin
remodeling
at
cell-cell
communication
loci.
Using
an
inference
approach,
revealed
signaling
gene
modules
tissue-level
cross-talk,
including
a
neoplasia-driving
feedback
loop
between
discrete
epithelial
immune
populations
was
functionally
validated
mice.
Our
results
uncover
neoplasia-specific
tissue-remodeling
program
may
be
exploited
cancer
interception.
Cells,
Год журнала:
2023,
Номер
12(15), С. 1970 - 1970
Опубликована: Июль 30, 2023
Single-cell
RNA
sequencing
(scRNA-seq)
has
emerged
as
a
powerful
tool
for
investigating
cellular
biology
at
an
unprecedented
resolution,
enabling
the
characterization
of
heterogeneity,
identification
rare
but
significant
cell
types,
and
exploration
cell-cell
communications
interactions.
Its
broad
applications
span
both
basic
clinical
research
domains.
In
this
comprehensive
review,
we
survey
current
landscape
scRNA-seq
analysis
methods
tools,
focusing
on
count
modeling,
cell-type
annotation,
data
integration,
including
spatial
transcriptomics,
inference
communication.
We
review
challenges
encountered
in
analysis,
issues
sparsity
or
low
expression,
reliability
assumptions
discuss
potential
impact
suboptimal
clustering
differential
expression
tools
downstream
analyses,
particularly
identifying
subpopulations.
Finally,
recent
advancements
future
directions
enhancing
analysis.
Specifically,
highlight
development
novel
annotating
single-cell
data,
integrating
interpreting
multimodal
datasets
covering
epigenomics,
proteomics,
inferring
communication
networks.
By
elucidating
latest
progress
innovation,
provide
overview
rapidly
advancing
field
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Июнь 18, 2024
Abstract
Tumorigenesis
is
a
multistep
process,
with
oncogenic
mutations
in
normal
cell
conferring
clonal
advantage
as
the
initial
event.
However,
despite
pervasive
somatic
and
expansion
tissues,
their
transformation
into
cancer
remains
rare
event,
indicating
presence
of
additional
driver
events
for
progression
to
an
irreversible,
highly
heterogeneous,
invasive
lesion.
Recently,
researchers
are
emphasizing
mechanisms
environmental
tumor
risk
factors
epigenetic
alterations
that
profoundly
influencing
early
malignant
evolution,
independently
inducing
mutations.
Additionally,
evolution
tumorigenesis
reflects
multifaceted
interplay
between
cell-intrinsic
identities
various
cell-extrinsic
exert
selective
pressures
either
restrain
uncontrolled
proliferation
or
allow
specific
clones
progress
tumors.
by
which
induce
both
intrinsic
cellular
competency
remodel
stress
facilitate
not
fully
understood.
In
this
review,
we
summarize
genetic,
epigenetic,
external
events,
effects
on
co-evolution
transformed
cells
ecosystem
during
initiation
evolution.
A
deeper
understanding
earliest
molecular
holds
promise
translational
applications,
predicting
individuals
at
high-risk
developing
strategies
intercept
transformation.
Abstract
Sustained
chronic
inflammation
of
the
large
intestine
leads
to
tissue
damage
and
repair,
which
is
associated
with
an
increased
incidence
colitis-associated
colorectal
cancer
(CAC).
The
genetic
makeup
CAC
somewhat
similar
sporadic
carcinoma
(sCRC),
but
there
are
differences
in
sequence
timing
alterations
carcinogenesis
process.
Several
models
have
been
developed
explain
development
CAC,
particularly
“field
cancerization”
model,
proposes
that
accelerates
mutagenesis
selects
for
clonal
expansion
phenotypically
normal,
pro-tumorigenic
cells.
In
contrast,
“Big
Bang”
model
posits
tumorigenic
clones
multiple
driver
gene
mutations
emerge
spontaneously.
details
tumorigenesis—and
how
they
differ
from
sCRC—are
not
yet
fully
understood.
this
Review,
we
discuss
recent
genetic,
epigenetic,
environmental
findings
related
pathogenesis
past
five
years,
a
focus
on
unbiased,
high-resolution
profiling
non-dysplastic
field
cancerization
context
inflammatory
bowel
disease
(IBD).
Cell Reports Medicine,
Год журнала:
2024,
Номер
5(3), С. 101461 - 101461
Опубликована: Март 1, 2024
Pancreatic
ductal
adenocarcinoma
(PDAC)
remains
one
of
the
most
lethal
types
cancer,
and
novel
treatment
regimens
are
direly
needed.
Epigenetic
regulation
contributes
to
development
various
cancer
types,
but
its
role
in
potential
as
a
therapeutic
target
for
PDAC
underexplored.
Here,
we
show
that
PRMT1
is
highly
expressed
murine
human
pancreatic
essential
cell
proliferation
tumorigenesis.
Deletion
delays
KRAS-dependent
mouse
model,
multi-omics
analyses
reveal
depletion
leads
global
changes
chromatin
accessibility
transcription,
resulting
reduced
glycolysis
decrease
tumorigenic
capacity.
Pharmacological
inhibition
combination
with
gemcitabine
has
synergistic
effect
on
tumor
growth
vitro
vivo.
Collectively,
our
findings
implicate
key
regulator
promising
therapy.
