bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Авг. 18, 2022
Abstract
Cell
competition
is
a
developmental
phenomenon
that
allows
the
selection
of
healthier
cells
in
developing
tissue.
In
this
process,
with
reduced
fitness,
conceivably
due
to
harmful
mutations,
acquire
‘loser’
status
and
are
eliminated
by
fitter
(winner)
neighboring
via
juxtacrine
cell-cell
interactions.
How
various
mutations
trigger
cell
an
extensively
studied
question.
However,
mechanism
remains
largely
elusive.
study,
we
reveal
previously
unknown
functions
ER
Golgi
localized
protein
Rer1
regulation
Drosophila
wing
epithelium.
Our
data
show
loss
leads
proteotoxic
stress
marked
increased
phosphorylation
eIF2α.
The
rer1
mutant
led
their
elimination
competition.
Interestingly,
find
levels
upregulated
upon
Myc
overexpression,
which
generates
super-competitive
overgrow
at
expense
normal
cells.
Loss
also
restricts
growth
Myc-induced
Moreover,
consistent
its
known
function
as
negative
regulator
Notch
pathway,
our
results
Myc-overexpression
downregulation
activity.
summary,
these
observations
provide
first
characterization
role
triggering
stress.
Journal of Biological Chemistry,
Год журнала:
2024,
Номер
300(4), С. 107151 - 107151
Опубликована: Март 9, 2024
The
Integrated
Stress
Response
(ISR)
refers
to
signaling
pathways
initiated
by
stress-activated
eIF2‹
kinases.
Distinct
kinases
respond
different
stress
signals,
including
amino
acid
deprivation
and
mitochondrial
stress.
Such
stress-induced
phosphorylation
attenuates
general
mRNA
translation
and,
at
the
same
time,
stimulates
preferential
of
specific
downstream
factors
orchestrate
an
adaptive
gene
expression
program.
In
recent
years,
there
have
been
significant
new
advances
in
our
understanding
ISR
during
metabolic
adaptation.
Here,
I
discuss
those
advances,
reviewing
among
others
activation
mechanisms
response
addition,
review
how
regulates
changes
impact
physiology
pathology
various
disease
models.
ABSTRACT
Although
differential
transcription
drives
the
development
of
multicellular
organisms,
ultimate
readout
a
protein-coding
gene
is
ribosome-dependent
mRNA
translation.
Ribosomes
were
once
thought
as
uniform
molecular
machines,
but
emerging
evidence
indicates
that
complexity
and
diversity
ribosome
biogenesis
function
should
be
given
fresh
look
in
context
development.
This
Review
begins
with
discussion
different
developmental
disorders
have
been
linked
perturbations
production
function.
We
then
highlight
recent
studies
reveal
how
cells
tissues
exhibit
variable
levels
protein
synthesis,
changes
synthesis
capacity
can
influence
specific
cell
fate
decisions.
finish
by
touching
upon
heterogeneity
stress
responses
These
discussions
importance
considering
both
functional
specialization
disease.
PLoS Biology,
Год журнала:
2025,
Номер
23(1), С. e3003004 - e3003004
Опубликована: Янв. 27, 2025
The
role
of
epigenetics
and
chromatin
in
the
maintenance
postmitotic
neuronal
cell
identities
is
not
well
understood.
Here,
we
show
that
histone
methyltransferase
Trithorax
(Trx)
required
memory
neurons
Drosophila
mushroom
body
(MB)
to
enable
their
capacity
for
long-term
(LTM),
but
short-term
(STM).
Using
MB-specific
RNA-,
ChIP-,
ATAC-sequencing,
find
Trx
maintains
homeostatic
expression
several
non-canonical
MB-enriched
transcripts,
including
orphan
nuclear
receptor
Hr51,
metabolic
enzyme
lactate
dehydrogenase
(Ldh).
Through
these
key
targets,
facilitates
a
state
characterized
by
high
levels
MBγ
neurons.
This
supports
protein
translation,
process
essential
LTM,
STM.
These
data
suggest
Trx,
classic
regulator
type
specification
during
development,
has
additional
functions
maintaining
underappreciated
aspects
neuron
identity,
such
as
state.
Our
work
evidence
suggesting
energy
metabolism
an
identity
characteristic
mediate
LTM.
FEBS Letters,
Год журнала:
2024,
Номер
598(4), С. 379 - 389
Опубликована: Фев. 1, 2024
Multicellular
communities
have
an
intrinsic
mechanism
that
optimizes
their
structure
and
function
via
cell–cell
communication.
One
of
the
driving
forces
for
such
self‐organization
multicellular
system
is
cell
competition,
elimination
viable
unfit
or
deleterious
cells
interaction.
Studies
in
Drosophila
mammals
identified
multiple
mechanisms
competition
caused
by
different
types
mutations
cellular
changes.
Intriguingly,
recent
studies
found
“losers”
commonly
show
reduced
protein
synthesis.
In
,
reduction
synthesis
levels
loser
phosphorylation
translation
initiation
factor
eIF2α
a
bZip
transcription
Xrp1.
Given
variety
stresses
converge
on
thus
global
inhibition
synthesis,
may
be
machinery
fitness
removing
stressed
cells.
this
review,
we
summarize
discuss
emerging
signaling
critical
unsolved
questions,
as
well
role
competition.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Март 10, 2023
ABSTRACT
The
frequent
acquisition
of
genomic
abnormalities
in
human
preimplantation
embryos
is
a
leading
cause
pregnancy
loss,
but
does
not
necessarily
prohibit
healthy
offspring.
However,
the
impact
on
cellular
states
and
development
early
embryo
remains
largely
unclear.
Here,
we
characterise
aneuploidy
reconstruct
gene
regulatory
networks
embryos,
investigate
expression
developmental
perturbations
instigated
by
using
single-cell
genome-and-transcriptome
sequencing
(G&T-seq).
At
level,
show
that
acquired
numerical
structural
chromosomal
aberrations
are
across
all
stages
embryogenesis
cell
lineages.
transcriptome
identify
regulators
identity
uncover
network
248
transcription
factors
from
10
major
modules
distinct
lineages
embryos.
By
integrating
DNA-with
RNA-information,
unveil
how
levels
affected
losses
or
gains
corresponding
genes
embryonic
cells
development,
as
well
copy-number
aberrant
factor
perturb
their
cognate
target
euploid
regions.
Furthermore,
reveal
majority
aneuploid
delay
reduced
fitness,
indicating
competition
within
mosaic
diploid-aneuploid
embryo,
which
may
contribute
to
selection
against
birth
offspring
In
summary,
our
multi-modal
analyses
provide
unprecedented
insights
into
development.
PLoS Genetics,
Год журнала:
2021,
Номер
17(12), С. e1009946 - e1009946
Опубликована: Дек. 16, 2021
Cell
competition
induces
the
elimination
of
less-fit
“loser”
cells
by
fitter
“winner”
cells.
In
Drosophila
,
heterozygous
mutant
in
ribosome
genes,
Rp/+
known
as
Minutes
are
outcompeted
wild-type
display
proteotoxic
stress
and
oxidative
response,
which
drive
loser
status.
Minute
cell
also
requires
transcription
factors
Irbp18
Xrp1,
but
how
these
contribute
to
status
is
partially
understood.
Here
we
provide
evidence
that
initial
RpS3/+
Xrp1-independent.
However,
Xrp1
sufficient
induce
otherwise
necessary
for
high
levels
found
Surprisingly,
induced
downstream
stress,
required
competitive
suffering
from
or
overexpressing
Nrf2.
Our
data
suggests
a
feed-forward
loop
between
Nrf2
drives
become
losers.
PLoS Genetics,
Год журнала:
2021,
Номер
17(12), С. e1009958 - e1009958
Опубликована: Дек. 6, 2021
Cell
competition
is
a
context-dependent
cell
elimination
via
cell-cell
interaction
whereby
unfit
cells
(‘losers’)
are
eliminated
from
the
tissue
when
confronted
with
fitter
(‘winners’).
Despite
extensive
studies,
mechanism
that
drives
loser’s
death
and
its
physiological
triggers
remained
elusive.
Here,
through
genetic
screen
in
Drosophila
,
we
find
endoplasmic
reticulum
(ER)
stress
causes
competition.
Mechanistically,
ER
upregulates
bZIP
transcription
factor
Xrp1,
which
promotes
phosphorylation
of
eukaryotic
translation
initiation
eIF2α
kinase
PERK,
leading
to
elimination.
Surprisingly,
our
data
show
different
such
as
ribosomal
protein
mutations
or
RNA
helicase
Hel25E
converge
on
upregulation
leads
thus
reduction
global
synthesis
apoptosis
wild-type
cells.
These
findings
not
only
uncover
core
pathway
but
also
open
way
understanding
Abstract
Ribosomal
proteins
(Rps)
are
essential
for
viability.
Genetic
mutations
affecting
Rp
genes
were
first
discovered
in
Drosophila,
where
they
represent
a
major
class
of
haploinsufficient
mutations.
One
mutant
copy
gives
rise
to
the
dominant
“Minute”
phenotype,
characterized
by
slow
growth
and
small,
thin
bristles.
Wild-type
(WT)
Minute
cells
compete
mosaics,
that
is,
Rp+/−
preferentially
lost
when
their
neighbors
wild-type
genotype.
Many
features
gene
haploinsufficiency
(i.e.
phenotypes)
mediated
transcriptional
program.
In
reduced
translation
under
control
Xrp1,
bZip-domain
transcription
factor
induced
leads
ultimately
phosphorylation
eIF2α
consequently
inhibition
most
translation.
phenotypes
also
transcriptionally
yeast
mammals.
mammals,
Impaired
Ribosome
Biogenesis
Checkpoint
activates
p53.
Recent
findings
link
other
cellular
stresses,
including
DNA
damage
response
endoplasmic
reticulum
stress.
We
suggest
cell
competition
results
from
nonautonomous
inputs
stress
responses,
bringing
decisions
between
adaptive
apoptotic
outcomes
influence
nearby
cells.
eliminates
aneuploid
which
loss
chromosome
haploinsufficiency.
The
effects
on
whole
organism,
flies
or
humans
with
Diamond-Blackfan
Anemia,
may
be
inevitable
consequences
pathways
useful
eliminating
individual
mosaics.
Alternatively,
apparently
deleterious
organism
might
adaptive,
preventing
even
more
detrimental
outcomes.
example,
p53
activation
appears
suppress
oncogenic