bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 25, 2024
Abstract
Background
The
body’s
internal
milieu
is
controlled
by
a
system
of
interoceptors
coupled
to
motor
outflows
that
drive
compensatory
adaptive
responses.
These
include
the
arterial
chemoreceptors,
best
known
for
sensing
oxygen.
In
cardiometabolic
diseases,
such
as
essential
hypertension,
carotid
bodies
(CB)
exhibit
heightened
reflex
sensitivity
and
tonic
activity
without
an
apparent
stimulus.
mechanisms
behind
CB
sensitization
in
these
conditions
are
not
well
understood.
Methods
Guided
functional
genomics,
range
assays
used
interrogate
downstream
intracellular
interorgan
signalling
pathways
involved
chemosensory
function.
Results
Here,
we
report
presence
Melanocortin
4
receptor
(MC4R)
mammalian
show
its
elevated
expression
experimental
hypertension.
We
demonstrate
melanocortin
agonists
activate
cells,
modulating
afferent
influence
both
resting
chemoreflex-evoked
sympathetic
ventilatory
activity.
Transcriptional
analysis
hypertensive
implicates
activation
Mash1
(
Ascl1
)
regulatory
network
driving
Mc4r
expression.
Conclusions
Collectively,
our
data
indicate
primarily
pathophysiological
role
chemosensation,
contributing
excess
disease.
Abstract
ATP-dependent
switch/sucrose
nonfermenting-type
chromatin
remodeling
complexes
(SWI/SNF
CRCs)
are
multiprotein
machineries
altering
structure,
thus
controlling
the
accessibility
of
genomic
DNA
to
various
regulatory
proteins
including
transcription
factors
(TFs).
SWI/SNF
CRCs
highly
evolutionarily
conserved
among
eukaryotes.
There
three
main
subtypes
CRCs:
canonical
(cBAF),
polybromo
(pBAF),
and
noncanonical
(ncBAF)
in
humans
their
functional
Arabidopsis
counterparts
SYD-associated
(SAS),
MINU-associated
(MAS),
BRAHMA
(BRM)-associated
(BAS).
Here,
we
highlight
importance
interplay
between
TFs
human
summarize
recent
advances
demonstrating
role
important
processes.
We
discuss
possible
mechanisms
involved
CRCs-dependent
transcriptional
control
gene
expression.
indicate
that
may
serve
as
a
valuable
model
for
identification
SWI/SNF–TF
interactions
postulate
further
exploration
CRCs-interplay,
especially
context
particular
CRC
subtypes,
TF
type,
well
cell/tissue
conditions,
others,
will
help
address
questions
related
specificity
sequence
events
occurring
on
target
genes.
Graphical
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 9, 2024
Enteroendocrine
cells
(EECs),
which
secrete
serotonin
(enterochromaffin
cells,
EC)
or
a
dominant
peptide
hormone,
serve
vital
physiologic
functions.
As
with
any
adult
human
lineage,
the
basis
for
terminal
cell
diversity
remains
obscure.
We
replicated
EEC
differentiation
FEBS Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 22, 2025
Epigenetic
modifications
of
chromatin
are
essential
for
the
establishment
cell
identities
during
embryogenesis.
Between
embryonic
days
3.5–7.5
murine
development,
major
lineage
decisions
made
that
discriminate
extraembryonic
and
tissues,
primary
germ
layers
formed,
thereby
laying
down
basic
body
plan.
In
this
review,
we
cover
contribution
dynamic
by
DNA
methylation,
changes
accessibility,
histone
modifications,
in
combination
with
transcription
factors
control
gene
expression
programs
different
types.
We
highlight
differences
regulation
enhancer
promoter
marks
discuss
their
requirement
specification.
Importantly,
many
cases,
lineage‐specific
targeting
epigenetic
modifiers
is
carried
out
pioneer
or
master
factors,
sum
mediate
landscape
cell‐type‐specific
thus,
identities.
Retinal
Müller
glia
in
cold-blooded
vertebrates
can
reprogram
into
neurogenic
progenitors
to
replace
neurons
lost
injury,
but
mammals
lack
this
ability.
While
recent
studies
have
shown
that
transgenic
overexpression
of
bHLH
factors
and
glial-specific
disruption
NFI
family
transcription
Notch
signaling
induce
competence
mammalian
glia,
induction
neurogenesis
wildtype
has
thus
far
proven
elusive.
Here
we
report
viral-mediated
the
pluripotency
factor
Oct4
(
Pou5f1
)
induces
transdifferentiation
mouse
bipolar
neurons,
synergistically
stimulates
glial-derived
parallel
with
loss
function.
Single
cell
multiomic
analysis
shows
leads
widespread
changes
gene
expression
chromatin
accessibility,
inducing
activity
both
Rfx4
Yamanaka
Sox2
Klf4.
This
study
demonstrates
retinal
Muller
identifying
mechanisms
could
be
used
cell-based
therapies
for
treating
dystrophies.
Retinal
Müller
glia
in
cold-blooded
vertebrates
can
reprogram
into
neurogenic
progenitors
to
replace
neurons
lost
injury,
but
mammals
lack
this
ability.
While
recent
studies
have
shown
that
transgenic
overexpression
of
bHLH
factors
and
glial-specific
disruption
NFI
family
transcription
Notch
signaling
induce
competence
mammalian
glia,
induction
neurogenesis
wildtype
has
thus
far
proven
elusive.
Here
we
report
viral-mediated
the
pluripotency
factor
Oct4
(
Pou5f1
)
induces
transdifferentiation
mouse
bipolar
neurons,
synergistically
stimulates
glial-derived
parallel
with
loss
function.
Single
cell
multiomic
analysis
shows
leads
widespread
changes
gene
expression
chromatin
accessibility,
inducing
activity
both
Rfx4
Yamanaka
Sox2
Klf4.
This
study
demonstrates
retinal
Muller
identifying
mechanisms
could
be
used
cell-based
therapies
for
treating
dystrophies.