Cell Discovery,
Journal Year:
2022,
Volume and Issue:
8(1)
Published: July 19, 2022
The
clear
cell
renal
carcinoma
(ccRCC)
microenvironment
consists
of
many
different
types
and
structural
components
that
play
critical
roles
in
cancer
progression
drug
resistance,
but
the
cellular
architecture
underlying
gene
regulatory
features
ccRCC
have
not
been
fully
characterized.
Here,
we
applied
single-cell
RNA
sequencing
(scRNA-seq)
assay
for
transposase-accessible
chromatin
(scATAC-seq)
to
generate
transcriptional
epigenomic
landscapes
ccRCC.
We
identified
tumor
cell-specific
programs
mediated
by
four
key
transcription
factors
(TFs)
(HOXC5,
VENTX,
ISL1,
OTP),
these
TFs
prognostic
significance
Cancer
Genome
Atlas
(TCGA)
database.
Targeting
via
short
hairpin
RNAs
(shRNAs)
or
small
molecule
inhibitors
decreased
proliferation.
next
performed
an
integrative
analysis
accessibility
expression
CD8+
T
cells
macrophages
reveal
elements
their
subgroups.
Furthermore,
delineated
intercellular
communications
ligand-receptor
interactions
within
microenvironment.
Taken
together,
our
multiomics
approach
further
clarifies
heterogeneity
identifies
potential
therapeutic
targets.
Journal of Clinical Investigation,
Journal Year:
2023,
Volume and Issue:
133(4)
Published: Feb. 14, 2023
Kidney
disease
is
a
major
driver
of
mortality
among
patients
with
diabetes
and
diabetic
kidney
(DKD)
responsible
for
close
to
half
all
chronic
cases.
DKD
usually
develops
in
genetically
susceptible
individual
as
result
poor
metabolic
(glycemic)
control.
Molecular
genetic
studies
indicate
the
key
role
podocytes
endothelial
cells
driving
albuminuria
early
diabetes.
Proximal
tubule
changes
show
strong
association
glomerular
filtration
rate.
Hyperglycemia
represents
cellular
stress
by
altering
metabolism
imposing
an
excess
workload
requiring
energy
oxygen
proximal
cells.
Changes
induce
adaptive
hypertrophy
reorganization
actin
cytoskeleton.
Later,
mitochondrial
defects
contribute
increased
oxidative
activation
inflammatory
pathways,
causing
progressive
function
decline
fibrosis.
Blockade
renin-angiotensin
system
or
sodium-glucose
cotransporter
associated
protection
slowing
decline.
Newly
identified
molecular
pathways
could
provide
basis
development
much-needed
novel
therapeutics.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: April 15, 2021
Abstract
Determining
the
epigenetic
program
that
generates
unique
cell
types
in
kidney
is
critical
for
understanding
cell-type
heterogeneity
during
tissue
homeostasis
and
injury
response.
Here,
we
profile
open
chromatin
gene
expression
developing
adult
mouse
kidneys
at
single
resolution.
We
show
reliance
of
on
distal
regulatory
elements
(enhancers).
reveal
key
type-specific
transcription
factors
major
gene-regulatory
circuits
cells.
Dynamic
changes
nephron
progenitor
differentiation
demonstrates
podocyte
commitment
occurs
early
associated
with
sustained
Foxl1
expression.
Renal
tubule
cells
follow
a
more
complex
differentiation,
where
Hfn4a
proximal
Tfap2b
fate.
Mapping
nucleotide
variants
human
disease
implicates
types,
developmental
stages,
genes,
mechanisms.
The
multi-omics
atlas
reveals
remodeling
events
dynamics
development.
Annual Review of Physiology,
Journal Year:
2021,
Volume and Issue:
84(1), P. 507 - 531
Published: Nov. 29, 2021
The
kidney
maintains
electrolyte,
water,
and
acid-base
balance,
eliminates
foreign
waste
compounds,
regulates
blood
pressure,
secretes
hormones.
There
are
at
least
16
different
highly
specialized
epithelial
cell
types
in
the
mammalian
kidney.
number
of
endothelial
cells,
immune
interstitial
might
even
be
larger.
concerted
interplay
between
is
critical
for
function.
Traditionally,
cells
were
defined
by
their
function
or
microscopical
morphological
appearance.
With
advent
new
single-cell
modalities
such
as
transcriptomics,
epigenetics,
metabolomics,
proteomics
we
entering
into
a
era
type
definition.
This
technological
revolution
provides
opportunities
to
classify
understand
functions.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: July 11, 2022
The
kidney
has
tremendous
capacity
to
repair
after
acute
injury,
however,
pathways
guiding
adaptive
and
fibrotic
are
poorly
understood.
We
developed
a
model
of
regeneration
by
titrating
ischemic
injury
dose.
performed
detailed
biochemical
histological
analysis
profiled
transcriptomic
changes
at
bulk
single-cell
level
(>
110,000
cells)
over
time.
Our
highlights
proximal
tubule
cells
as
key
susceptible
injury.
Adaptive
correlated
with
fatty
acid
oxidation
oxidative
phosphorylation.
identify
specific
maladaptive/profibrotic
cluster
long
ischemia,
which
expresses
proinflammatory
profibrotic
cytokines
myeloid
cell
chemotactic
factors.
Druggability
pyroptosis/ferroptosis
vulnerable
in
these
cells.
Pharmacological
targeting
vivo
pushed
towards
ameliorates
fibrosis.
In
summary,
our
defines
differences
identifies
druggable
for
pharmacological
intervention
prevent
