Hepatology,
Journal Year:
2023,
Volume and Issue:
80(3), P. 698 - 720
Published: April 1, 2023
Single-cell
transcriptomics
enables
the
identification
of
rare
cell
types
and
inference
state
transitions,
whereas
spatially
resolved
allows
quantification
cells
genes
in
context
tissues.
The
recent
progress
these
new
technologies
is
improving
our
understanding
landscape
its
roles
diseases.
Here,
we
review
key
biological
insights
into
liver
homeostasis,
development,
regeneration,
chronic
disease,
cancer
obtained
from
single-cell
transcriptomics.
We
highlight
atlas
that
characterizes
comprehensive
cellular
composition;
diversity
function;
spatial
architecture
such
as
zonation,
communication,
proximity;
identity
conversion
cell-specific
alterations
are
associated
with
pathology;
therapeutic
targets.
further
discuss
outstanding
challenges,
advanced
experimental
technologies,
computational
methods
help
to
address
challenges.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Sept. 12, 2023
Abstract
Liver
sinusoidal
endothelial
cells
(LSECs)
play
a
pivotal
role
in
maintaining
liver
homeostasis
and
influencing
the
pathological
processes
of
various
diseases.
However,
neither
LSEC-specific
hallmark
genes
nor
LSEC
promoter-driven
Cre
mouse
line
has
been
introduced
before,
which
largely
restricts
study
diseases
with
vascular
disorders.
To
explore
genes,
we
compared
top
50
marker
between
(ECs)
capillary
ECs
identified
18
overlapping
genes.
After
excluding
globally
expressed
those
low
expression
percentages,
narrowed
our
focus
to
two
final
candidates:
Oit3
Dnase1l3.
Through
single-cell
RNA
sequencing
(scRNA-seq)
analysis
NCBI
database,
confirmed
extrahepatic
The
paired-cell
data
further
demonstrated
that
was
predominantly
midlobular
ECs.
Subsequently,
constructed
inducible
Oit3-CreERT2
transgenic
mice,
were
crossed
ROSA26-tdTomato
mice.
Microscopy
validated
established
Oit3-CreERT2-tdTomato
mice
exhibited
significant
fluorescence
rather
than
other
organs.
staining
colocalization
tdTomato
EC
markers.
Ex-vivo
experiments
isolated
tdTomato+
well-differentiated
fenestrae
highly
markers,
confirming
their
identity
as
LSECs.
Overall,
is
promising
gene
for
tracing
establishment
provides
valuable
model
studying
complexities
LSECs
Hepatology Communications,
Journal Year:
2024,
Volume and Issue:
8(3)
Published: Feb. 14, 2024
NAFLD
is
highly
prevalent
with
limited
treatment
options.
Bile
acids
(BAs)
increase
in
the
systemic
circulation
and
liver
during
progression.
Changes
plasma
membrane
localization
zonal
distribution
of
BA
transporters
can
influence
transport
function
homeostasis.
However,
a
thorough
characterization
how
influences
these
factors
currently
lacking.
This
study
aimed
to
evaluate
impact
accompanying
histologic
features
on
functional
capacity
key
hepatocyte
across
regions
human
biopsies.
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(26)
Published: June 28, 2024
Liver
fibrosis
is
characterized
by
the
activation
of
perivascular
hepatic
stellate
cells
(HSCs),
release
fibrogenic
nanosized
extracellular
vesicles
(EVs),
and
increased
HSC
glycolysis.
Nevertheless,
how
glycolysis
in
HSCs
coordinates
amplification
through
tissue
zone-specific
pathways
remains
elusive.
Here,
we
demonstrate
that
HSC-specific
genetic
inhibition
reduced
liver
fibrosis.
Moreover,
spatial
transcriptomics
revealed
a
fibrosis-mediated
up-regulation
EV-related
pericentral
zone,
which
was
abrogated
inhibition.
Mechanistically,
up-regulated
expression
genes
such
as
Ras-related
protein
Rab-31
(
RAB31
)
enhancing
histone
3
lysine
9
acetylation
on
promoter
region,
EV
release.
Functionally,
these
glycolysis-dependent
EVs
fibrotic
gene
recipient
HSC.
Furthermore,
derived
from
glycolysis-deficient
mice
contrast
to
glycolysis-competent
mouse
EVs.
In
summary,
amplifies
promoting
represents
potential
therapeutic
target.
Hepatology,
Journal Year:
2023,
Volume and Issue:
80(3), P. 698 - 720
Published: April 1, 2023
Single-cell
transcriptomics
enables
the
identification
of
rare
cell
types
and
inference
state
transitions,
whereas
spatially
resolved
allows
quantification
cells
genes
in
context
tissues.
The
recent
progress
these
new
technologies
is
improving
our
understanding
landscape
its
roles
diseases.
Here,
we
review
key
biological
insights
into
liver
homeostasis,
development,
regeneration,
chronic
disease,
cancer
obtained
from
single-cell
transcriptomics.
We
highlight
atlas
that
characterizes
comprehensive
cellular
composition;
diversity
function;
spatial
architecture
such
as
zonation,
communication,
proximity;
identity
conversion
cell-specific
alterations
are
associated
with
pathology;
therapeutic
targets.
further
discuss
outstanding
challenges,
advanced
experimental
technologies,
computational
methods
help
to
address
challenges.
