Molecular Therapy,
Journal Year:
2021,
Volume and Issue:
30(4), P. 1741 - 1753
Published: Oct. 22, 2021
Angiotensin
receptor
blockers
(ARBs)
and
sodium-glucose
cotransporter
2
inhibitors
(SGLT2i)
have
been
used
as
the
standard
therapy
for
patients
with
diabetic
kidney
disease
(DKD).
However,
how
these
two
drugs
possess
additive
renoprotective
effects
remains
unclear.
Here,
we
conducted
single-cell
RNA
sequencing
to
profile
cell
transcriptome
of
db/db
mice
treated
vehicle,
ARBs,
SGLT2i,
or
ARBs
plus
using
db/m
control.
We
identified
10
distinct
clusters
cells
predominant
proximal
tubular
(PT)
cells.
found
that
had
more
anti-inflammatory
anti-fibrotic
effects,
while
SGLT2i
affected
mitochondrial
function
in
PT.
also
a
new
PT
subcluster,
was
increased
DKD,
but
reversed
by
treatments.
This
subcluster
confirmed
immunostaining
mouse
human
kidneys
DKD.
Together,
our
study
reveals
cell-specific
gene
signatures
response
identifies
which
provides
insight
into
pathogenesis
Nature Cardiovascular Research,
Journal Year:
2022,
Volume and Issue:
1(3), P. 263 - 280
Published: March 16, 2022
Heart
failure
represents
a
major
cause
of
morbidity
and
mortality
worldwide.
Single-cell
transcriptomics
have
revolutionized
our
understanding
cell
composition
associated
gene
expression.
Through
integrated
analysis
single-cell
single-nucleus
RNA-sequencing
data
generated
from
27
healthy
donors
18
individuals
with
dilated
cardiomyopathy,
here
we
define
the
failing
human
heart.
We
identify
cell-specific
transcriptional
signatures
age
heart
reveal
emergence
disease-associated
states.
Notably,
cardiomyocytes
converge
toward
common
states,
whereas
fibroblasts
myeloid
cells
undergo
dramatic
diversification.
Endothelial
pericytes
display
global
shifts
without
changes
in
complexity.
Collectively,
findings
provide
comprehensive
cellular
transcriptomic
landscape
failure,
type-specific
programs
states
establish
valuable
resource
for
investigation
failure.
Proceedings of the National Academy of Sciences,
Journal Year:
2021,
Volume and Issue:
118(27)
Published: June 28, 2021
Significance
A
single
acute
kidney
injury
event
increases
the
risk
of
progression
to
chronic
disease
(CKD).
Combining
single-nucleus
RNA
sequencing
with
genetic
tracing
injured
proximal
tubule
cells
identified
a
spatially
dynamic,
evolving
response
following
ischemia–reperfusion
injury.
Failed
repair
leads
persistence
profibrotic,
proinflammatory
Vcam1
+
/
Ccl2
cell
type
exhibiting
senescence-associated
secretory
phenotype
and
marked
transcriptional
activation
NF-κB
AP-1
pathway
signatures,
but
no
signs
G
2
/M
cycle
arrest.
Insights
from
this
study
can
inform
strategies
improve
renal
prevent
CKD
progression.
Frontiers in Endocrinology,
Journal Year:
2022,
Volume and Issue:
13
Published: May 25, 2022
Diabetic
nephropathy
(DN)
and
diabetic
retinopathy
(DR)
are
microvascular
complications
of
diabetes.
Microvascular
endothelial
cells
thought
to
be
the
major
targets
hyperglycemic
injury.
In
microvasculature,
intracellular
hyperglycemia
causes
damages
vascular
endothelium,
via
multiple
pathophysiological
process
consist
inflammation,
cell
crosstalk
with
podocytes/pericytes
exosomes.
addition,
DN
DR
diseases
development
involved
in
several
critical
regulators
including
adhesion
molecules
(CAMs),
growth
factor
(VEGF)
family
Notch
signal.
The
present
review
attempts
gain
a
deeper
understanding
pathogenesis
complexities
underlying
dysfunction
diabetes
retinopathy,
contributing
new
mechanistic
therapeutic
strategies
against
diabetes-induced
dysfunction.
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.
Overwhelming
lipid
peroxidation
induces
ferroptotic
stress
and
ferroptosis,
a
non-apoptotic
form
of
regulated
cell
death
that
has
been
implicated
in
maladaptive
renal
repair
mice
humans.
Using
single-cell
transcriptomic
mouse
genetic
approaches,
we
show
proximal
tubular
(PT)
cells
develop
molecularly
distinct,
pro-inflammatory
state
following
injury.
While
these
inflammatory
PT
transiently
appear
after
mild
injury
return
to
their
original
without
inducing
fibrosis,
severe
they
accumulate
contribute
persistent
inflammation.
This
transient
significantly
downregulates
glutathione
metabolism
genes,
making
the
vulnerable
stress.
Genetic
induction
high
leads
accumulation
cells,
enhancing
inflammation
fibrosis.
Our
study
broadens
roles
from
being
trigger
include
promotion
proinflammatory
underlie
repair.
Journal of the American Society of Nephrology,
Journal Year:
2023,
Volume and Issue:
34(4), P. 554 - 571
Published: Jan. 13, 2023
Significance
Statement
Understanding
the
mechanisms
underlying
adaptive
and
maladaptive
renal
repair
after
AKI
their
long-term
consequences
is
critical
to
kidney
health.
The
authors
used
lineage
tracing
of
cycling
cells
single-nucleus
multiomics
(profiling
transcriptome
chromatin
accessibility)
AKI.
They
demonstrated
that
triggers
a
cell-cycle
response
in
most
epithelial
nonepithelial
cell
types.
also
showed
proinflammatory
proximal
tubule
(PTCs)
persist
until
6
months
post-AKI,
although
they
decreased
abundance
over
time,
part,
through
death.
Single-nucleus
lineage-traced
revealed
regulatory
features
repair.
These
included
activation
state–specific
transcription
factors
cis-regulatory
elements,
effects
PTCs
even
repair,
weeks
injury
event.
Background
proliferative
as
part
an
intrinsic
cellular
program,
which
can
lead
restoring
structure
function,
or
with
persistence
injured
altered
structure.
However,
molecular
understanding
these
programs
limited.
Methods
To
examine
transcriptional
responses
same
upon
ischemia-reperfusion
(IRI),
we
combined
genetic
fate
mapping
(
Ki67
+
)
labeled
early
IRI
multiomics—profiling
accessibility
nucleus—and
generated
dataset
83,315
nuclei.
Results
triggered
broad
cycle
preceded
by
type–specific
global
changes
nephron,
collecting
vascular
systems,
stromal
immune
We
observed
heterogeneous
population
throughout
segments
marked
loss
from
4
months.
Gene
expression
profiling
nuclei
highlighted
differences
between
activity
elements
factors,
accompanied
corresponding
target
gene
expression.
Adaptive
was
associated
reduced
genes
encoding
transmembrane
transport
proteins
essential
function.
Conclusions
Analysis
genome
organization
single-cell
resolution
using
offers
new
insight
into
regulation
Weeks
mild-to-moderate
IRI,
aberrant
epigenetic
landscape,
exhibit
profile
following