bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 5, 2024
Abstract
To
elucidate
the
aging-associated
cellular
population
dynamics
throughout
body,
here
we
present
PanSci,
a
single-cell
transcriptome
atlas
profiling
over
20
million
cells
from
623
mouse
tissue
samples,
encompassing
range
of
organs
across
different
life
stages,
sexes,
and
genotypes.
This
comprehensive
dataset
allowed
us
to
identify
more
than
3,000
unique
states
catalog
200
distinct
cell
populations
experiencing
significant
depletion
or
expansion.
Our
panoramic
analysis
uncovered
temporally
structured,
organ-
lineage-specific
shifts
during
lifespan
progression.
Moreover,
investigated
alterations
in
immune
populations,
revealing
both
widespread
organ-specific
changes.
We
further
explored
regulatory
roles
system
on
aging
pinpointed
specific
age-related
expansions
that
are
lymphocyte-dependent.
The
breadth
depth
our
‘cell-omics’
methodology
not
only
enhance
comprehension
but
also
lay
groundwork
for
exploring
complex
networks
among
varied
types
context
diseases.
One
Sentence
Summary
lifespan,
unveils
temporal
architecture
dynamics,
shifts,
lymphocyte’s
role
organismal
aging.
Journal of Tissue Engineering,
Journal Year:
2025,
Volume and Issue:
16
Published: Jan. 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,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 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
Stem Cell Research & Therapy,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: May 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.
Nucleic Acids Research,
Journal Year:
2024,
Volume and Issue:
52(19), P. 11481 - 11499
Published: Sept. 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
Cells,
Journal Year:
2024,
Volume and Issue:
13(24), P. 2052 - 2052
Published: Dec. 12, 2024
Cellular
rejuvenation
therapies
represent
a
transformative
frontier
in
addressing
age-related
decline
and
extending
human
health
span.
By
targeting
fundamental
hallmarks
of
aging—such
as
genomic
instability,
epigenetic
alterations,
mitochondrial
dysfunction,
cellular
senescence—these
aim
to
restore
youthful
functionality
cells
tissues,
offering
new
hope
for
treating
degenerative
diseases.
Recent
advancements
have
showcased
range
strategies,
including
reprogramming,
senolytic
interventions,
restoration,
stem
cell-based
approaches,
gene-editing
technologies
like
CRISPR.
Each
modality
has
demonstrated
substantial
potential
preclinical
models
is
now
being
cautiously
explored
early-stage
clinical
trials.
However,
translating
these
from
the
laboratory
practice
presents
unique
challenges:
safety
concerns,
delivery
precision,
complex
regulatory
requirements,
ethical
considerations,
high
costs
impede
widespread
adoption.
This
review
examines
current
landscape
rejuvenation,
highlighting
key
advancements,
risks,
strategies
needed
overcome
hurdles.
The Journals of Gerontology Series A,
Journal Year:
2024,
Volume and Issue:
79(7)
Published: May 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
