Cell Death and Disease,
Год журнала:
2024,
Номер
15(2)
Опубликована: Фев. 19, 2024
Unlike
most
cancer
types,
the
incidence
of
esophageal
adenocarcinoma
(EAC)
has
rapidly
escalated
in
western
world
over
recent
decades.
Using
whole
genome
bisulfite
sequencing
(WGBS),
we
identify
transcription
factor
(TF)
FOXM1
as
an
important
epigenetic
regulator
EAC.
plays
a
critical
role
cellular
proliferation
and
tumor
growth
EAC
patient-derived
organoids
cell
line
models.
We
ERBB2
upstream
expression
transcriptional
activity
FOXM1.
Unexpectedly,
gene
set
enrichment
analysis
(GSEA)
unbiased
screen
reveals
prominent
anti-correlation
between
immune
response
pathways.
Indeed,
syngeneic
mouse
models
show
that
inhibits
infiltration
CD8
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(44)
Опубликована: Сен. 15, 2023
The
accurate,
rapid,
and
sensitive
identification
of
cancer
cells
in
complex
physiological
environments
is
significant
biological
studies,
personalized
medicine,
biomedical
engineering.
Inspired
by
the
naturally
confined
enzymes
on
fluid
cell
membranes,
a
fluidly
CRISPR-based
DNA
reporter
(FINDER)
was
developed
living
which
successfully
applied
for
rapid
clinical
blood
samples.
Benefiting
from
spatial
confinement
effect
improved
local
concentration,
membrane
fluidity
higher
collision
efficiency,
activity
CRISPR-Cas12a
was,
first
time,
found
to
be
significantly
enhanced
membranes.
This
new
phenomenon
then
combined
with
multiple
aptamer-based
logic
gate
recognition,
thus
FINDER
system
capable
constructed.
rapidly
identified
target
only
20
min,
achieved
over
80
%
recognition
efficiency
0.1
presented
samples,
indicating
its
potential
application
Abstract
CDKN2A
is
a
tumor
suppressor
located
in
chromosome
9p21
and
frequently
lost
Barrett’s
esophagus
(BE)
esophageal
adenocarcinoma
(EAC).
How
other
gene
co-deletions
affect
EAC
evolution
remains
understudied.
We
explored
the
effects
of
loss
EACs
cancer
progressor
non-progressor
BEs
with
matched
genomic,
transcriptomic
clinical
data.
Despite
its
driver
role,
BE
prevents
initiation
by
counterselecting
subsequent
TP53
alterations.
predict
poor
patient
survival
but
not
through
context-dependent
on
cell
cycle,
oxidative
phosphorylation
interferon
response.
Immune
quantifications
using
bulk
transcriptome,
RNAscope
high-dimensional
tissue
imaging
showed
that
IFNE
reduces
immune
infiltration
BE,
EAC.
Mechanistically,
suppresses
maintenance
squamous
epithelium,
contributing
to
more
aggressive
phenotype.
Our
study
demonstrates
roles
genes
during
disease
evolution,
consequences
for
detection
management.
Nucleic Acids Research,
Год журнала:
2025,
Номер
53(2)
Опубликована: Янв. 11, 2025
Abstract
The
expansion
of
single-cell
analytical
techniques
has
empowered
the
exploration
diverse
biological
questions
at
individual
cells.
Droplet-based
RNA
sequencing
(scRNA-seq)
methods
have
been
particularly
widely
used
due
to
their
high-throughput
capabilities
and
small
reaction
volumes.
While
commercial
systems
contributed
widespread
adoption
droplet-based
scRNA-seq,
relatively
high
cost
limits
ability
profile
large
numbers
cells
samples.
Moreover,
as
scale
continues
expand,
accommodating
workflows
cost-effective
multi-biospecimen
profiling
becomes
more
critical.
Herein,
we
present
inDrops-2,
an
open-source
scRNA-seq
technology
designed
live
or
preserved
with
a
sensitivity
matching
that
state-of-the-art
but
6-fold
lower
cost.
We
demonstrate
flexibility
by
implementing
two
prominent
protocols,
based
on
exponential
linear
amplification
barcoded-complementary
DNA,
provide
useful
insights
into
advantages
disadvantages
inherent
each
approach.
applied
inDrops-2
simultaneously
multiple
human
lung
carcinoma
samples
had
subjected
cell
preservation,
long-term
storage
multiplexing
obtain
multiregional
cellular
tumor
microenvironment.
scalability,
efficiency
make
stand
out
among
other
methods,
ideal
for
large-scale
studies
rare
molecular
signatures.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Апрель 20, 2022
Abstract
Although
morphologic
progression
coupled
with
expression
of
specific
molecular
markers
has
been
characterized
along
the
esophageal
squamous
differentiation
gradient,
heterogeneity
within
cell
types
this
trajectory
yet
to
be
classified
at
single
level.
To
address
knowledge
gap,
we
perform
RNA-sequencing
44,679
murine
epithelial,
identify
11
distinct
populations
as
well
pathways
alterations
basal-superficial
axis
and
in
each
individual
population.
We
evaluate
impact
aging
upon
epithelial
demonstrate
age-associated
mitochondrial
dysfunction.
compare
transcriptomic
profiles
3D
organoids
human
biopsies
that
epithelium.
Finally,
employ
pseudotemporal
analysis
develop
a
working
model
fate
determination
These
studies
provide
comprehensive
perspective
on
cellular
epithelium
context
homeostasis
aging.
Abstract
Immune
checkpoint
blockade
has
recently
proven
effective
in
subsets
of
patients
with
esophageal
adenocarcinoma
(EAC)
but
little
is
known
regarding
the
EAC
immune
microenvironment.
We
determined
single
cell
transcriptional
profile
8
who
were
treatment-naive
(
n
=
4)
or
had
received
neoadjuvant
chemotherapy
4).
Analysis
52,387
cells
revealed
10
major
tumor,
and
stromal
cells.
Prior
to
tumors
heavy
infiltrated
by
T
regulatory
exhausted
effector
whilst
plasmacytoid
dendritic
markedly
expanded.
Two
dominant
cancer-associated
fibroblast
populations
also
observed
endothelial
suppressed.
Pathological
remission
following
associated
broad
reversal
abnormalities
together
transition
an
increase
a
chemoresistant
epithelial
stem
population
correlated
poor
response.
These
findings
reveal
features
that
underlie
limit
response
current
immunotherapy
identify
range
novel
opportunities
for
targeted
therapy.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Сен. 27, 2022
Abstract
Digestive
system
diseases
arise
primarily
through
the
interplay
of
genetic
and
environmental
influences;
there
is
an
urgent
need
in
elucidating
pathogenic
mechanisms
these
deploy
personalized
treatments.
Traditional
long-established
model
systems
rarely
reproduce
either
tissue
complexity
or
human
physiology
faithfully;
shortcomings
underscore
for
better
models.
Organoids
represent
a
promising
research
model,
helping
us
gain
more
profound
understanding
digestive
organs;
this
can
also
be
used
to
provide
patients
with
precise
individualized
treatment
build
rapid
vitro
test
models
drug
screening
gene/cell
therapy,
linking
basic
clinical
treatment.
Over
past
few
decades,
use
organoids
has
led
advanced
composition
each
organ
facilitated
disease
modeling,
chemotherapy
dose
prediction,
CRISPR-Cas9
intervention,
high-throughput
screening,
identification
SARS-CoV-2
targets,
infection.
However,
existing
mainly
include
epithelial
system.
In
order
reveal
mechanism
diseases,
it
necessary
establish
completer
physiological
organoid
model.
Combining
techniques
treatments
different
formulations
approach
that
requires
further
exploration.
This
review
highlights
advancements
field
technology
from
perspectives
modeling
therapy.