Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Май 20, 2019
Abstract
Sparse
populations
of
neurons
in
the
dentate
gyrus
(DG)
hippocampus
are
causally
implicated
encoding
contextual
fear
memories.
However,
engram-specific
molecular
mechanisms
underlying
memory
consolidation
remain
largely
unknown.
Here
we
perform
unbiased
RNA
sequencing
DG
engram
24
h
after
conditioning
to
identify
transcriptome
changes
specific
consolidation.
exhibit
a
highly
distinct
pattern
gene
expression,
which
CREB-dependent
transcription
features
prominently
(
P
=
6.2
×
10
−13
),
including
Atf3
2.4
−41
Penk
1.3
−15
and
Kcnq3
3.1
−12
).
Moreover,
validate
functional
relevance
RNAseq
findings
by
establishing
causal
requirement
intact
CREB
function
specifically
within
during
consolidation,
novel
group
target
genes
involved
long-term
memory.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Сен. 28, 2021
Differential
expression
analysis
in
single-cell
transcriptomics
enables
the
dissection
of
cell-type-specific
responses
to
perturbations
such
as
disease,
trauma,
or
experimental
manipulations.
While
many
statistical
methods
are
available
identify
differentially
expressed
genes,
principles
that
distinguish
these
and
their
performance
remain
unclear.
Here,
we
show
relative
is
contingent
on
ability
account
for
variation
between
biological
replicates.
Methods
ignore
this
inevitable
biased
prone
false
discoveries.
Indeed,
most
widely
used
can
discover
hundreds
genes
absence
differences.
To
exemplify
principles,
exposed
true
discoveries
injured
mouse
spinal
cord.
The
coordinated
spatial
and
temporal
regulation
of
gene
expression
in
the
vertebrate
neural
tube
determines
identity
progenitors
function
physiology
neurons
they
generate.
Progress
has
been
made
deciphering
regulatory
programmes
that
are
responsible
for
this
process;
however,
complexity
tissue
hampered
systematic
analysis
network
underlying
mechanisms.
To
address
this,
we
used
single
cell
mRNA
sequencing
to
profile
cervical
thoracic
regions
developing
mouse
between
embryonic
days
9.5-13.5.
We
confirmed
data
accurately
recapitulates
development,
allowing
us
identify
new
markers
specific
progenitor
neuronal
populations.
In
addition,
highlighted
a
previously
underappreciated
component
mechanisms
generate
diversity,
revealed
common
features
sequence
transcriptional
events
lead
differentiation
subtypes.
Together,
offer
insight
into
specification
provide
compendium
classifying
spinal
cord
types
will
support
future
studies
disease.
ABSTRACT
The
vertebrate
spinal
cord
comprises
multiple
functionally
distinct
neuronal
cell
types
arranged
in
characteristic
positions.
During
development,
these
different
of
neurons
differentiate
from
transcriptionally
neural
progenitors
that
are
arrayed
discrete
domains
along
the
dorsal-ventral
and
anterior-posterior
axes
embryonic
cord.
This
organization
arises
response
to
morphogen
gradients
acting
upstream
a
gene
regulatory
network,
architecture
which
determines
spatial
temporal
pattern
expression.
In
recent
years,
substantial
progress
has
been
made
deciphering
network
underlies
specification
progenitor
identities.
this
Review,
we
outline
how
identities
established
patterning
systems,
novel
experimental
approaches
study
emergence
function
diversity
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Янв. 7, 2019
Abstract
The
development
of
the
mammalian
cerebral
cortex
depends
on
careful
orchestration
proliferation,
maturation,
and
migration
events,
ultimately
giving
rise
to
a
wide
variety
neuronal
non-neuronal
cell
types.
To
better
understand
cellular
molecular
processes
that
unfold
during
late
corticogenesis,
we
perform
single-cell
RNA-seq
mouse
at
progenitor
driven
phase
(embryonic
day
14.5)
birth—after
neurons
from
all
six
cortical
layers
are
born.
We
identify
numerous
classes
neurons,
progenitors,
glia,
their
proliferative,
migratory,
activation
states,
relatedness
within
across
age.
Using
cell-type-specific
expression
patterns
genes
mutated
in
neurological
psychiatric
diseases,
putative
disease
subtypes
associate
with
clinical
phenotypes.
Our
study
reveals
template
complex
neurodevelopmental
process,
provides
window
into
origins
brain
diseases.
The Journal of Experimental Medicine,
Год журнала:
2021,
Номер
218(8)
Опубликована: Июнь 16, 2021
The
wound
healing
process
that
occurs
after
spinal
cord
injury
is
critical
for
maintaining
tissue
homeostasis
and
limiting
damage,
but
eventually
results
in
a
scar-like
environment
not
conducive
to
regeneration
repair.
A
better
understanding
of
this
dichotomy
developing
effective
therapeutics
target
the
appropriate
pathobiology,
major
challenge
has
been
large
cellular
heterogeneity
immensely
complex
interactions.
In
study,
we
used
single-cell
RNA
sequencing
assess
virtually
all
cell
types
comprise
mouse
site.
addition
discovering
novel
subpopulations,
expression
values
receptor–ligand
pairs
identify
signaling
pathways
are
predicted
regulate
specific
interactions
during
angiogenesis,
gliosis,
fibrosis.
Our
dataset
valuable
resource
provides
mechanistic
insight
into
pathobiology
only
also
other
traumatic
disorders
CNS.
Cell Reports,
Год журнала:
2020,
Номер
30(4), С. 1246 - 1259.e6
Опубликована: Янв. 1, 2020
Age-related
macular
degeneration
(AMD)
is
a
leading
cause
of
vision
loss.
To
better
understand
disease
pathogenesis
and
identify
causal
genes
in
GWAS
loci
for
AMD
risk,
we
present
comprehensive
database
human
retina
retinal
pigment
epithelium
(RPE).
Our
comprises
non-macular
RNA
sequencing
(RNA-seq)
profiles
from
129
donors,
genome-wide
expression
quantitative
trait
(eQTL)
dataset
that
includes
macula-specific
RPE/choroid,
single-nucleus
RNA-seq
(NucSeq)
RPE
with
subtype
resolution
more
than
100,000
cells.
Using
NucSeq,
find
enriched
candidate
We
15
putative
on
the
basis
co-localization
genetic
association
signals
risk
eye
eQTL,
including
TSPAN10
TRPM1.
These
results
demonstrate
value
our
elucidating
pathways
potential
therapeutic
targets
ocular
diseases.
