Stem Cell Research & Therapy,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 5, 2024
The
effectiveness
of
adipose-derived
stem
cells
(ADSCs)
in
therapy
diminishes
with
age.
It
has
been
reported
that
transcription
factors
(TFs)
play
a
crucial
role
the
aging
and
functionality
cells.
Nevertheless,
there
is
limited
understanding
regarding
involvement
TFs
mechanism
ADSCs.
RNA
sequencing
(RNA-seq)
was
utilized
to
discern
differentially
expressed
genes
ADSCs
obtained
from
donors
varying
ages.
exhibiting
significant
variations
across
age
groups
were
identified
subsequently
validated.
manipulated
exhibit
either
enhanced
expression
or
reduced
levels
HES1
STAT1
via
lentivirus
transfection
small
interfering
(siRNA)
techniques.
impact
these
genetic
alterations
on
ADSCs'
proliferation,
migration,
cellular
senescence
assessed
using
EdU,
transwell,
senescence-activated
β-galactosidase
(SA-β-gal)
staining
assays.
DNA
sequences
bound
by
investigated
through
CUT
&
Tag
assay.
Lastly,
therapeutic
efficacy
aged
overexpression
evaluated
skin
injury
model
male
Sprague-Dawley
rats.
678
showed
differential
between
young
old
(Y-ADSCs
O-ADSCs),
47
being
TFs.
Notably,
TF
hairy
enhancer
split
1
(HES1)
notably
donors.
Introducing
resulted
improved
function
suppression
senescence,
while
reducing
had
opposite
effect.
Mechanistically,
found
interact
promoter
region
another
TF,
signal
transducer
activator
(STAT1),
inhibit
its
transcription.
Knocking
down
could
fully
reverse
negative
effects
caused
decreased
ADSCs,
leading
reduction
secretion
pro-inflammatory
cytokines
such
as
TNF-α,
IL-6,
IL-8.
Ultimately,
restoring
demonstrated
potential
promoting
wound
healing.
acts
an
inhibitor
progression
modulation
expression,
suggesting
promising
avenue
for
rejuvenating
senescent
improving
Journal of Tissue Engineering,
Год журнала:
2025,
Номер
16
Опубликована: Янв. 1, 2025
Bone
marrow
stimulation
treatment
by
bone
stromal
cells
(BMSCs)
released
from
the
medullary
cavity
and
differentiated
into
cartilage
via
microfracture
surgery
is
a
frequently
employed
technique
for
treating
articular
injuries,
yet
presents
main
drawback
of
poor
regeneration
in
elderly.
Prior
research
indicated
that
aging
could
decrease
stemness
capacity
BMSCs,
thus
we
made
hypothesis
increasing
old
BMSCs
(OBMSCs)
might
improve
results
First,
investigated
correlation
between
outcomes
using
clinical
data
animal
experiments.
The
elderly
were
significantly
decreased
as
compared
with
young
counterparts
while
OBMSCs
was
also
decreased,
they
positively
correlated.
To
investigate
role
microfracture,
developed
microfracture-mimic
organoid
models.
In
vitro
experiments
identified
SPI1
potential
target
gene,
which
enhance
chondrogenesis
OBMSCs.
implantation
organoids
SPI1-overexpressed
notably
rats
alone.
Furthermore,
molecular
docking
suggested
possible
interaction
5-Aza-2′-deoxycytidine
(5Aza).
application
5Aza
result
upregulating
SPI1.
summary,
novel
OBMSCs,
beneficial
improvement
microfracture-stimulated
Stem Cell Research & Therapy,
Год журнала:
2025,
Номер
16(1)
Опубликована: Май 5, 2025
Recent
studies
have
suggested
that
targeting
senescent
cells
in
joint
tissues
may
alleviate
osteoarthritis
(OA)
progression.
However,
this
strategy
encounters
significant
challenges,
partially
due
to
the
high
degree
of
cellular
heterogeneity
osteoarthritic
tissues.
Moreover,
little
information
is
available
on
role
skeletal
stem
cell
(SSC)
senescence,
as
compared
differentiated
cells,
OA
In
study,
single-cell
RNA
sequencing
(scRNA-seq)
articular
cartilages
and
subchondral
bones
knee
joints
mice
with
post-traumatic
(PTOA)
were
performed.
Further
vivo
vitro
performed
reveal
mechanisims
SSCs
during
development
lesions
progression
by
microCT,
pathological
analysis,
functional
gain
loss
experiments.
The
one-way
ANOVA
was
used
multiple
group
data
analysis.
scRNA-seq
demonstrated
leptin
receptors
(Lepr)
positive
underwent
senescence
addition,
leptin-Lepr
signaling
pathway
induced
signal
transducer
activator
transcription
3
(STAT3)
expression
SSCs,
which
consequently
augmented
fibroblast
growth
factor
7
(FGF7).
analyses
revealed
FGF7
exacerbated
abnormal
bone
remodeling
enhancing
formation
suppressing
resorption.
analysis
osteogenic
differentiation
but
inhibited
osteoclastogenesis
a
concentration-dependent
manner.
summary,
our
findings
demonstrate
promotes
SSC
exacerbates
activating
STAT3-FGF7
axis
progression,
shed
light
novel
therapeutic
strategies
for
OA.
Stem Cell Research & Therapy,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 19, 2024
Abstract
Due
to
the
rapid
development
of
stem
cell
technology,
there
have
been
tremendous
advances
in
molecular
biological
and
pathological
research,
therapy
as
well
organoid
technologies
over
past
decades.
Advances
genome
editing
particularly
discovery
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)
CRISPR-related
protein
9
(Cas9),
further
facilitated
researches.
The
CRISPR-Cas9
technology
now
goes
beyond
creating
single
gene
enable
inhibition
or
activation
endogenous
loci
by
fusing
inhibitory
(CRISPRi)
activating
(CRISPRa)
domains
with
deactivated
Cas9
proteins
(dCas9).
These
tools
utilized
genome-scale
CRISPRi/a
screen
recognize
hereditary
modifiers
that
are
synergistic
opposing
malady
mutations
an
orderly
fair
manner,
thereby
identifying
illness
mechanisms
discovering
novel
restorative
targets
accelerate
medicinal
investigation.
However,
application
this
technique
is
still
relatively
rare
research.
There
numerous
specialized
challenges
applying
large-scale
useful
genomics
approaches
differentiated
populations.
Here,
we
present
first
comprehensive
review
on
CRISPR-based
functional
screening
field
cells,
practical
considerations
implemented
a
range
scenarios,
exploration
insights
into
fates,
disease
treatments
models.
This
will
broadly
benefit
scientists,
engineers
medical
practitioners
areas
Nucleic Acids Research,
Год журнала:
2024,
Номер
52(19), С. 11481 - 11499
Опубликована: Сен. 11, 2024
Dysfunction
of
the
ribosome
manifests
during
cellular
senescence
and
contributes
to
tissue
aging,
functional
decline,
development
aging-related
disorders
in
ways
that
have
remained
enigmatic.
Here,
we
conducted
a
comprehensive
CRISPR-based
loss-of-function
(LOF)
screen
ribosome-associated
genes
(RAGs)
human
mesenchymal
progenitor
cells
(hMPCs).
Through
this
approach,
identified
ribosomal
protein
L22
(RPL22)
as
foremost
RAG
whose
deficiency
mitigates
effects
senescence.
Consequently,
absence
RPL22
delays
hMPCs
from
becoming
senescent,
while
an
excess
accelerates
process.
Mechanistically,
found
senescent
hMPCs,
accumulates
within
nucleolus.
This
accumulation
triggers
cascade
events,
including
heterochromatin
decompaction
with
concomitant
degradation
key
proteins,
specifically
1γ
(HP1γ)
KRAB-associated
1
(KAP1).
Subsequently,
RPL22-dependent
breakdown
stimulates
transcription
RNAs
(rRNAs),
triggering
In
summary,
our
findings
unveil
novel
role
for
nucleolar
destabilizer
driver
senescence,
shedding
new
light
on
intricate
mechanisms
underlying
aging
The Journals of Gerontology Series A,
Год журнала:
2024,
Номер
79(7)
Опубликована: Май 18, 2024
Abstract
Epigenetic
changes
have
been
established
to
be
a
hallmark
of
aging,
which
implies
that
aging
science
requires
collaborating
with
the
field
chromatin
biology.
DNA
methylation
patterns,
in
relative
abundance
histone
post-translational
modifications,
and
remodeling
are
central
players
modifying
structure.
Aging
is
commonly
associated
an
overall
increase
instability,
loss
homeostasis,
decondensation.
However,
numerous
publications
highlighted
link
between
not
nearly
as
linear
previously
expected.
This
complex
interplay
these
epigenetic
elements
during
lifetime
organism
likely
contributes
cellular
senescence,
genomic
disease
susceptibility.
Yet,
causal
links
phenomena
still
need
fully
unraveled.
In
this
perspective
article,
we
discuss
potential
future
directions
