Genes & Development,
Год журнала:
2022,
Номер
36(3-4), С. 149 - 166
Опубликована: Фев. 1, 2022
The
process
of
tissue
regeneration
occurs
in
a
developmentally
timed
manner,
yet
the
role
circadian
timing
is
not
understood.
Here,
we
identify
for
adult
muscle
stem
cell
(MuSC)-autonomous
clock
control
following
acute
ischemic
injury.
We
observed
greater
repair
capacity
injury
during
active/wake
period
as
compared
with
inactive/rest
mice,
and
loss
Bmal1
within
MuSCs
leads
to
impaired
regeneration.
demonstrate
that
reduced
activated
MuSC
number
at
day
3
postinjury,
indicating
failure
properly
expand
myogenic
precursor
pool.
In
cultured
primary
myoblasts,
impairs
proliferation
hypoxia
(a
condition
first
1–3
d
vivo),
well
subsequent
myofiber
differentiation.
Loss
both
myoblasts
vivo
glycolysis
premature
activation
prodifferentiation
gene
transcription
epigenetic
remodeling.
Finally,
hypoxic
formation
Bmal1-
deficient
are
restored
by
increasing
cytosolic
NAD
+
.
Together,
pivotal
regulator
oxygen-dependent
myoblast
fate
through
-driven
response
Nature,
Год журнала:
2022,
Номер
613(7942), С. 169 - 178
Опубликована: Дек. 21, 2022
Abstract
Tissue
regeneration
requires
coordination
between
resident
stem
cells
and
local
niche
1,2
.
Here
we
identify
that
senescent
are
integral
components
of
the
skeletal
muscle
regenerative
repress
at
all
stages
life.
The
technical
limitation
senescent-cell
scarcity
3
was
overcome
by
combining
single-cell
transcriptomics
a
enrichment
sorting
protocol.
We
identified
isolated
different
cell
types
from
damaged
muscles
young
old
mice.
Deeper
transcriptome,
chromatin
pathway
analyses
revealed
conservation
identity
traits
as
well
two
universal
senescence
hallmarks
(inflammation
fibrosis)
across
type,
time
ageing.
Senescent
create
an
aged-like
inflamed
mirrors
inflammation
associated
with
ageing
(inflammageing
4
)
arrests
proliferation
regeneration.
Reducing
burden
cells,
or
reducing
their
inflammatory
secretome
through
CD36
neutralization,
accelerates
in
By
contrast,
transplantation
delays
Our
results
provide
technique
for
isolating
vivo
define
blueprint
muscle,
uncover
unproductive
functional
interactions
niches
can
be
overcome.
As
also
accumulate
human
muscles,
our
findings
open
potential
paths
improving
repair
throughout
Nature,
Год журнала:
2024,
Номер
629(8010), С. 154 - 164
Опубликована: Апрель 22, 2024
Abstract
Muscle
atrophy
and
functional
decline
(sarcopenia)
are
common
manifestations
of
frailty
critical
contributors
to
morbidity
mortality
in
older
people
1
.
Deciphering
the
molecular
mechanisms
underlying
sarcopenia
has
major
implications
for
understanding
human
ageing
2
Yet,
progress
been
slow,
partly
due
difficulties
characterizing
skeletal
muscle
niche
heterogeneity
(whereby
myofibres
most
abundant)
obtaining
well-characterized
samples
3,4
Here
we
generate
a
single-cell/single-nucleus
transcriptomic
chromatin
accessibility
map
limb
muscles
encompassing
over
387,000
cells/nuclei
from
individuals
aged
15
99
years
with
distinct
fitness
levels.
We
describe
how
cell
populations
change
during
ageing,
including
emergence
new
people,
cell-specific
multicellular
network
features
(at
epigenetic
levels)
associated
these
changes.
On
basis
cross-comparison
genetic
data,
also
identify
key
elements
architecture
that
mark
susceptibility
sarcopenia.
Our
study
provides
identifying
targets
amenable
medical,
pharmacological
lifestyle
interventions
late
life.
