Dynamic
interactions
between
gut
mucosal
cells
and
the
external
environment
are
essential
to
maintain
homeostasis.
Enterochromaffin
(EC)
transduce
both
chemical
mechanical
signals
produce
5-hydroxytryptamine
mediate
disparate
physiological
responses.
However,
molecular
cellular
basis
for
functional
diversity
of
ECs
remains
be
adequately
defined.
Here,
we
integrated
single-cell
transcriptomics
with
spatial
image
analysis
identify
14
EC
clusters
that
topographically
organized
along
gut.
Subtypes
predicted
sensitive
forces
were
identified
express
distinct
transcription
factors
hormones.
A
Piezo2
+
population
in
distal
colon
was
endowed
a
distinctive
neuronal
signature.
Using
combination
genetic,
chemogenetic,
pharmacological
approaches,
demonstrated
required
normal
motility.
Our
study
constructs
map
offers
framework
deconvoluting
pleiotropic
functions.
Cell,
Год журнала:
2023,
Номер
186(16), С. 3368 - 3385.e18
Опубликована: Авг. 1, 2023
The
properties
of
dorsal
root
ganglia
(DRG)
neurons
that
innervate
the
distal
colon
are
poorly
defined,
hindering
our
understanding
their
roles
in
normal
physiology
and
gastrointestinal
(GI)
disease.
Here,
we
report
genetically
defined
subsets
colon-innervating
DRG
with
diverse
morphologic
physiologic
properties.
Four
neuron
populations
mechanosensitive
exhibit
distinct
force
thresholds
to
distension.
highest
threshold
population,
selectively
labeled
using
Bmpr1b
genetic
tools,
is
necessary
sufficient
for
behavioral
responses
high
distension,
which
partly
mediated
by
mechanosensory
ion
channel
Piezo2.
This
Aδ-HTMR
population
mediates
over-reactivity
distension
caused
inflammation
a
model
inflammatory
bowel
Thus,
like
cutaneous
mechanoreceptor
populations,
mechanoreceptors
anatomical
physiological
tile
space,
HTMRs
mediate
pathophysiological
revealing
target
therapeutic
intervention.
Neuron,
Год журнала:
2023,
Номер
111(14), С. 2184 - 2200.e7
Опубликована: Май 15, 2023
Vagal
sensory
neurons
monitor
mechanical
and
chemical
stimuli
in
the
gastrointestinal
tract.
Major
efforts
are
underway
to
assign
physiological
functions
many
distinct
subtypes
of
vagal
neurons.
Here,
we
use
genetically
guided
anatomical
tracing,
optogenetics,
electrophysiology
identify
characterize
neuron
expressing
Prox2
Runx3
mice.
We
show
that
three
these
neuronal
innervate
esophagus
stomach
regionalized
patterns,
where
they
form
intraganglionic
laminar
endings.
Electrophysiological
analysis
revealed
low-threshold
mechanoreceptors
but
possess
different
adaptation
properties.
Lastly,
genetic
ablation
demonstrated
their
essential
roles
for
esophageal
peristalsis
freely
behaving
Our
work
defines
identity
function
provide
mechanosensory
feedback
from
brain
could
lead
better
understanding
treatment
motility
disorders.
Cells,
Год журнала:
2024,
Номер
13(6), С. 492 - 492
Опубликована: Март 12, 2024
Amyotrophic
lateral
sclerosis
(ALS)
is
a
mysterious
lethal
multisystem
neurodegenerative
disease
that
gradually
leads
to
the
progressive
loss
of
motor
neurons.
A
recent
non-contact
dying-back
injury
mechanism
theory
for
ALS
proposed
primary
damage
an
acquired
irreversible
intrafusal
proprioceptive
terminal
Piezo2
channelopathy
with
underlying
genetic
and
environmental
risk
factors.
Underpinning
this
excessively
prolonged
mechanotransduction
under
allostasis
may
induce
dysfunctionality
in
mitochondria,
leading
channelopathy.
This
microinjury
suggested
provide
one
gateway
from
physiology
pathophysiology.
The
chronic,
but
not
irreversible,
form
implicated
many
diseases
unknown
etiology.
Dry
eye
them
where
replenishing
synthetic
proteoglycans
promote
nerve
regeneration.
Syndecans,
especially
syndecan-3,
are
as
first
critical
link
hierarchical
ordered
depletory
pathomechanism
proton-collecting/distributing
antennas;
hence,
they
play
role
onset.
Even
more
importantly,
shedding
or
charge-altering
variants
Syndecan-3
contribute
channelopathy-induced
disruption
Piezo2-initiated
proton-based
ultrafast
long-range
signaling
through
VGLUT1
VGLUT2.
Thus,
these
alterations
only
cause
hippocampus
conscious
proprioception,
could
disrupt
feedback
motoneurons.
Correspondingly,
inert
signaled
skeletal
system
coming
light
be
progressively
lost
ALS.
In
addition,
functional
MyoD
family
inhibitor
proteins,
auxiliary
subunits
Piezo2,
theorized
channelopathy,
explain
how
microinjured
ion
channels
evolve
principal
transcription
activators.
Frontiers in Physiology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 6, 2024
The
intestine
is
the
largest
mechanosensitive
organ
in
human
body
whose
epithelial
cells,
smooth
muscle
neurons
and
enteroendocrine
cells
must
sense
respond
to
various
mechanical
stimuli
such
as
motility,
distension,
stretch
shear
regulate
physiological
processes
including
digestion,
absorption,
secretion,
motility
immunity.
Piezo
channels
are
a
newly
discovered
class
of
ion
consisting
two
subtypes,
Piezo1
Piezo2.
widely
expressed
involved
pathological
processes.
present
review
summarizes
current
research
progress
on
expression,
function
regulation
intestine,
with
aim
providing
reference
for
future
development
therapeutic
strategies
targeting
channels.
