bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Sept. 10, 2022
Abstract
A
major
cause
of
human
deafness
and
vestibular
dysfunction
is
permanent
loss
the
mechanosensory
hair
cells
inner
ear.
In
non-mammalian
vertebrates
such
as
zebrafish,
regeneration
missing
can
occur
throughout
life.
While
a
comparative
approach
has
potential
to
reveal
basis
differential
regenerative
ability,
degree
which
ears
fish
mammals
share
common
supporting
cell
types
remains
unresolved.
Here
we
perform
single-cell
RNA
sequencing
zebrafish
ear
at
embryonic
through
adult
stages
catalog
diversity
non-sensory
cells.
We
identify
putative
progenitor
population
for
cells,
well
distinct
in
maculae
versus
cristae.
The
differ
from
those
described
lateral
line
system,
distributed
organ
most
studies
have
been
conducted.
maculae,
two
subtypes
that
gene
expression
with
mammalian
striolar
or
extrastriolar
situ
hybridization
reveals
these
occupy
spatial
domains
within
macular
organs,
utricle
saccule,
consistent
reported
electrophysiological
properties
domains.
These
findings
suggest
primitive
specialization
spatially
likely
arose
last
ancestor
mammals.
similarities
type
composition
between
also
support
using
relevant
model
understanding
ear-specific
function
regeneration.
A
major
cause
of
human
deafness
and
vestibular
dysfunction
is
permanent
loss
the
mechanosensory
hair
cells
inner
ear.
In
non-mammalian
vertebrates
such
as
zebrafish,
regeneration
missing
can
occur
throughout
life.
While
a
comparative
approach
has
potential
to
reveal
basis
differential
regenerative
ability,
degree
which
ears
fish
mammals
share
common
supporting
cell
types
remains
unresolved.
Here,
we
perform
single-cell
RNA
sequencing
zebrafish
ear
at
embryonic
through
adult
stages
catalog
diversity
non-sensory
cells.
We
identify
putative
progenitor
population
for
cells,
well
distinct
in
maculae
versus
cristae.
The
differ
from
those
described
lateral
line
system,
distributed
organ
most
studies
have
been
conducted.
maculae,
two
subtypes
that
gene
expression
with
mammalian
striolar
or
extrastriolar
situ
hybridization
reveals
these
occupy
spatial
domains
within
three
macular
organs,
utricle,
saccule,
lagena,
consistent
reported
electrophysiological
properties
domains.
These
findings
suggest
primitive
specialization
spatially
likely
arose
last
ancestor
mammals.
similarities
type
composition
between
validate
relevant
model
understanding
ear-specific
function
regeneration.
Cell Reports,
Journal Year:
2021,
Volume and Issue:
35(2), P. 108978 - 108978
Published: April 1, 2021
The
human
fallopian
tube
harbors
the
cell
of
origin
for
majority
high-grade
serous
"ovarian"
cancers
(HGSCs),
but
its
cellular
composition,
particularly
epithelial
component,
is
poorly
characterized.
We
perform
single-cell
transcriptomic
profiling
around
53,000
individual
cells
from
12
primary
specimens
to
map
their
major
types.
identify
10
subpopulations
with
diverse
transcriptional
programs.
Based
on
signatures,
we
reconstruct
a
trajectory
whereby
secretory
differentiate
into
ciliated
via
RUNX3high
intermediate.
Computational
deconvolution
advanced
HGSCs
identifies
"early
secretory"
population
as
likely
precursor
state
HGSCs.
Its
signature
comprises
both
and
mesenchymal
features
enriched
in
mesenchymal-type
(p
=
6.7
×
10−27),
group
known
have
poor
prognoses.
This
molecular
compendium
cancer-free
women
expected
advance
our
understanding
earliest
stages
neoplasia.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Oct. 24, 2022
Otolith
organs
of
the
inner
ear
are
innervated
by
two
parallel
afferent
projections
to
brainstem
and
cerebellum.
These
innervations
were
proposed
segregate
across
line
polarity
reversal
(LPR)
within
each
otolith
organ,
which
divides
organ
into
regions
hair
cells
(HC)
with
opposite
stereociliary
orientation.
The
relationship
functional
significance
these
anatomical
features
not
known.
Here,
we
show
regional
expression
Emx2
in
organs,
establishes
LPR,
mediates
neuronal
segregation
LPR
constitutes
bidirectional
sensitivity
function.
Conditional
knockout
(cKO)
HCs
lacks
LPR.
Tmie
cKO,
mechanotransduction
was
abolished
selectively
domain
also
sensitivity.
Analyses
both
mutants
indicate
that
is
specifically
required
for
mice
swim
comfortably
traverse
a
balance
beam
efficiently,
but
stay
on
rotating
rod.
The
vestibular
maculae
of
the
inner
ear
contain
sensory
receptor
hair
cells
that
detect
linear
acceleration
and
contribute
to
equilibrioception
coordinate
posture
ambulatory
movements.
These
are
divided
between
two
groups,
separated
by
a
line
polarity
reversal
(LPR),
with
oppositely
oriented
planar-polarized
stereociliary
bundles
motion
in
opposite
directions.
transcription
factor
EMX2
is
known
establish
this
planar
polarized
organization
mouse
regulating
distribution
transmembrane
GPR156
at
cell
boundaries
one
group
cells.
However,
genes
regulated
context
were
previously
not
known.
Using
as
model,
we
have
identified
serine
threonine
kinase
STK32A
downstream
effector
negatively
EMX2.
Stk32a
expressed
on
side
LPR
pattern
complementary
Emx2
expression
side.
necessary
align
intrinsic
bundle
core
(PCP)
proteins
EMX2-negative
regions,
sufficient
reorient
when
ectopically
neighboring
EMX2-positive
regions.
We
demonstrate
reinforces
formation
apical
localization
GPR156.
observations
support
model
which
orientation
determined
through
separate
mechanisms
sides
maculae,
EMX2-mediated
repression
determining
final
position
LPR.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(2), P. 708 - 708
Published: Jan. 15, 2025
The
lateral
line
system
in
fish
is
crucial
for
detecting
water
flow,
which
facilitates
various
behaviors
such
as
prey
detection,
predator
avoidance,
and
rheotaxis.
cupula,
a
gelatinous
structure
overlaying
the
hair
cells
neuromasts,
plays
key
role
transmitting
mechanical
stimuli
to
cells.
However,
molecular
composition
of
cupula
matrix
remains
poorly
understood.
In
this
study,
we
found
that
Mucin-5AC,
novel
family
mucin
proteins,
composed
2–27
cysteine-rich
domains,
presents
cartilaginous
bony
fishes.
Using
situ
hybridization
transgenic
reporter
assays,
demonstrated
zebrafish
muc5AC
specifically
expressed
support
neuromasts.
Knockdown
via
antisense
morpholino
resulted
shorter
cupulae
line.
Additionally,
generated
mutants
using
CRISPR/Cas9
were
significantly
than
wild-types,
but
cell
number
neuromasts
was
not
changed
obviously.
Furthermore,
mutant
larvae
displayed
compromised
sensitivity
vibration
compared
wild-type
larvae.
This
study
provides
first
evidence
linking
gene
development
detection
zebrafish.
Our
findings
suggest
Mucin-5AC
likely
critical
component
matrix,
offering
an
important
clue
fish.
Eye & ENT Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 23, 2025
Abstract
Due
to
the
limited
regenerative
capacity
in
adult
mammals,
loss
of
vestibular
hair
cells
(HCs)
leads
balance
disorders.
In
this
study,
we
chronologically
reprogrammed
supporting
(SCs)
via
bimodal
regulation
Notch
signaling,
mimicking
dynamic
changes
signaling
during
inner
ear
development.
We
found
that
activating
stimulated
SC
proliferation
damaged
utricles,
priming
these
with
potential
regenerate
sensory
HCs.
Subsequent
inhibition
removed
lateral
barriers,
promoting
transition
from
proliferating
SCs
Our
findings
underscore
crucial
role
HC
regeneration.
Each
hair
cell
(HC)
precursor
of
zebrafish
neuromasts
divides
to
form
two
daughter
HCs
opposite
bundle
orientations.
Previously,
we
showed
that
transcription
factor
Emx2,
expressed
in
only
one
the
HCs,
generates
this
bidirectional
HC
pattern
(Jiang
et
al.,
2017).
Here,
asked
whether
Emx2
mediates
effect
by
changing
location
establishment
or
positions
since
are
known
switch
with
each
other.
We
rearrangement,
redefined
as
processes
named
Rock
and
Roll,
is
required
for
positional
acquisition
HCs.
Apical
protrusion
formation
nascent
planar
polarity
signaling
both
important
Roll.
facilitates
Roll
delaying
apical
its
but
it
does
not
determine
HCs’
ultimate
positions,
indicating
where
established
