Molecular Cell,
Год журнала:
2023,
Номер
83(17), С. 3205 - 3216.e5
Опубликована: Авг. 31, 2023
N6-methyladenosine
(m6A)
RNA
modification
plays
important
roles
in
the
governance
of
gene
expression
and
is
temporally
regulated
different
cell
states.
In
contrast
to
global
m6A
profiling
bulk
sequencing,
single-cell
technologies
for
analyzing
heterogeneity
are
not
extensively
established.
Here,
we
developed
single-nucleus
m6A-CUT&Tag
(sn-m6A-CT)
simultaneous
methylomes
transcriptomes
within
a
single
nucleus
using
mouse
embryonic
stem
cells
(mESCs).
m6A-CT
capable
enriching
m6A-marked
molecules
situ,
without
isolating
RNAs
from
cells.
We
adapted
droplet-based
omics
platform
demonstrated
high-throughput
performance
nuclei
isolated
thousands
various
types.
show
that
sn-m6A-CT
sufficient
determine
identity
allows
generation
cell-type-specific
methylome
landscapes
heterogeneous
populations.
These
indicate
provides
additional
dimensions
multimodal
datasets
insights
into
epitranscriptomic
landscape
defining
fate
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Июнь 18, 2024
Abstract
Tumorigenesis
is
a
multistep
process,
with
oncogenic
mutations
in
normal
cell
conferring
clonal
advantage
as
the
initial
event.
However,
despite
pervasive
somatic
and
expansion
tissues,
their
transformation
into
cancer
remains
rare
event,
indicating
presence
of
additional
driver
events
for
progression
to
an
irreversible,
highly
heterogeneous,
invasive
lesion.
Recently,
researchers
are
emphasizing
mechanisms
environmental
tumor
risk
factors
epigenetic
alterations
that
profoundly
influencing
early
malignant
evolution,
independently
inducing
mutations.
Additionally,
evolution
tumorigenesis
reflects
multifaceted
interplay
between
cell-intrinsic
identities
various
cell-extrinsic
exert
selective
pressures
either
restrain
uncontrolled
proliferation
or
allow
specific
clones
progress
tumors.
by
which
induce
both
intrinsic
cellular
competency
remodel
stress
facilitate
not
fully
understood.
In
this
review,
we
summarize
genetic,
epigenetic,
external
events,
effects
on
co-evolution
transformed
cells
ecosystem
during
initiation
evolution.
A
deeper
understanding
earliest
molecular
holds
promise
translational
applications,
predicting
individuals
at
high-risk
developing
strategies
intercept
transformation.
Skeletal
muscle
stem
cells
(also
known
as
satellite
[SCs])
are
essential
for
regeneration
and
the
regenerative
activities
of
SCs
intrinsically
governed
by
gene
regulatory
mechanisms,
but
post-transcriptional
regulation
in
remains
largely
unknown.
N(6)-methyladenosine
(m6A)
modification
RNAs
is
most
pervasive
highly
conserved
RNA
eukaryotic
cells;
it
exerts
powerful
impact
on
almost
all
aspects
mRNA
processing
that
mainly
endowed
its
binding
with
m6A
reader
proteins.
In
this
study,
we
investigate
previously
uncharacterized
roles
YTHDC1,
an
mouse
SCs.
Our
results
demonstrate
YTHDC1
regulator
SC
activation
proliferation
upon
acute
injury-induced
regeneration.
The
induction
indispensable
proliferation;
thus,
inducible
depletion
abolishes
capacity.
Mechanistically,
transcriptome-wide
profiling
using
LACE-seq
both
C2C12
myoblasts
identifies
m6A-mediated
targets
YTHDC1.
Next,
splicing
analysis
defines
m6A-YTHDC1.
Furthermore,
nuclear
export
also
leads
to
identification
potential
m6A-YTHDC1
myoblasts;interestingly,
some
mRNAs
can
be
regulated
at
levels.
Lastly,
map
interacting
protein
partners
unveil
a
myriad
factors
governing
splicing,
export,
transcription,
among
which
hnRNPG
appears
bona
fide
partner
Altogether,
our
findings
uncover
factor
controlling
ability
through
multifaceted
mechanisms
myoblast
cells.
Abstract
RNA
N
6
‐methyladenine
(m
A)
modification
represents
a
pivotal
epigenetic
that
facilitates
the
remodeling
of
gene
expression
and
regulates
variety
biological
processes
via
certain
post‐transcriptional
mechanisms.
However,
specific
function
m
A
in
insect
male
reproduction
remains
unclear.
In
this
study,
we
explored
molecular
mechanism
by
which
METTL3/METTL14‐mediated
invasive
pest
Bactrocera
dorsalis
.
The
results
showed
BdMettl3
BdMettl14
were
highly
expressed
fat
body
(FB)
accessory
glands
(MAGs).
Knockout
or
decreased
level
B.
,
resulting
testicular
deformities
significant
reduction
viable
sperm
number.
Specifically,
knockout
reduced
titer
20‐hydroxyecdysone
(20E,
active
form
ecdysone)
males.
messenger
(mRNA)
Disembodied
one
20E
synthesis
genes,
was
modified
A,
its
increased
20E.
mRNA
obviously
after
suggesting
testis
development
fecundity
modulating
synthesis.
Taken
together,
study
indicates
presents
new
regulatory
for
serving
as
potential
target
control
