Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Фев. 23, 2024
Abstract
Protein
translation
is
a
tightly
regulated
cellular
process
that
essential
for
gene
expression
and
protein
synthesis.
The
deregulation
of
this
increasingly
recognized
as
critical
factor
in
the
pathogenesis
various
human
diseases.
In
review,
we
discuss
how
deregulated
can
lead
to
aberrant
synthesis,
altered
functions,
disease
progression.
We
explore
key
mechanisms
contributing
translation,
including
functional
alterations
factors,
tRNA,
mRNA,
ribosome
function.
Deregulated
leads
abnormal
expression,
disrupted
signaling,
perturbed
functions-
all
which
contribute
pathogenesis.
development
profiling
techniques
along
with
mass
spectrometry-based
proteomics,
mRNA
sequencing
single-cell
approaches
have
opened
new
avenues
detecting
diseases
related
errors.
Importantly,
highlight
recent
advances
therapies
targeting
translation-related
disorders
their
potential
applications
neurodegenerative
diseases,
cancer,
infectious
cardiovascular
Moreover,
growing
interest
lies
targeted
aimed
at
restoring
precise
control
over
diseased
cells
discussed.
conclusion,
comprehensive
review
underscores
role
its
therapeutic
target.
Advancements
understanding
molecular
deregulation,
coupled
therapies,
offer
promising
improving
outcomes
Additionally,
it
will
unlock
doors
possibility
precision
medicine
by
offering
personalized
deeper
underpinnings
future.
Cell,
Год журнала:
2021,
Номер
184(24), С. 5985 - 6001.e19
Опубликована: Ноя. 1, 2021
Current
catalogs
of
regulatory
sequences
in
the
human
genome
are
still
incomplete
and
lack
cell
type
resolution.
To
profile
activity
gene
elements
diverse
types
tissues
body,
we
applied
single-cell
chromatin
accessibility
assays
to
30
adult
tissue
from
multiple
donors.
We
integrated
these
datasets
with
previous
data
15
fetal
reveal
status
open
for
∼1.2
million
candidate
cis-regulatory
(cCREs)
222
distinct
comprised
>1.3
nuclei.
used
maps
delineate
cell-type-specificity
cCREs
systematically
interpret
noncoding
variants
associated
complex
traits
diseases.
This
rich
resource
provides
a
foundation
analysis
programs
across
tissues,
life
stages,
organ
systems.
Nature,
Год журнала:
2022,
Номер
610(7931), С. 319 - 326
Опубликована: Окт. 12, 2022
Abstract
Self-organizing
neural
organoids
represent
a
promising
in
vitro
platform
with
which
to
model
human
development
and
disease
1–5
.
However,
lack
the
connectivity
that
exists
vivo,
limits
maturation
makes
integration
other
circuits
control
behaviour
impossible.
Here
we
show
stem
cell-derived
cortical
transplanted
into
somatosensory
cortex
of
newborn
athymic
rats
develop
mature
cell
types
integrate
sensory
motivation-related
circuits.
MRI
reveals
post-transplantation
organoid
growth
across
multiple
lines
animals,
whereas
single-nucleus
profiling
shows
progression
corticogenesis
emergence
activity-dependent
transcriptional
programs.
Indeed,
neurons
display
more
complex
morphological,
synaptic
intrinsic
membrane
properties
than
their
counterparts,
enables
discovery
defects
derived
from
individuals
Timothy
syndrome.
Anatomical
functional
tracings
receive
thalamocortical
corticocortical
inputs,
vivo
recordings
activity
demonstrate
these
inputs
can
produce
responses
cells.
Finally,
extend
axons
throughout
rat
brain
optogenetic
activation
drive
reward-seeking
behaviour.
Thus,
engage
host
We
anticipate
this
approach
will
be
useful
for
detecting
circuit-level
phenotypes
patient-derived
cells
cannot
otherwise
uncovered.
Nature,
Год журнала:
2023,
Номер
616(7955), С. 113 - 122
Опубликована: Март 15, 2023
Abstract
Emerging
spatial
technologies,
including
transcriptomics
and
epigenomics,
are
becoming
powerful
tools
for
profiling
of
cellular
states
in
the
tissue
context
1–5
.
However,
current
methods
capture
only
one
layer
omics
information
at
a
time,
precluding
possibility
examining
mechanistic
relationship
across
central
dogma
molecular
biology.
Here,
we
present
two
technologies
spatially
resolved,
genome-wide,
joint
epigenome
transcriptome
by
cosequencing
chromatin
accessibility
gene
expression,
or
histone
modifications
(H3K27me3,
H3K27ac
H3K4me3)
expression
on
same
section
near-single-cell
resolution.
These
were
applied
to
embryonic
juvenile
mouse
brain,
as
well
adult
human
map
how
epigenetic
mechanisms
control
transcriptional
phenotype
cell
dynamics
tissue.
Although
highly
concordant
features
identified
either
also
observed
distinct
patterns,
suggesting
their
differential
roles
defining
states.
Linking
pixel
allows
uncovering
new
insights
priming,
differentiation
regulation
within
architecture.
great
interest
life
science
biomedical
research.
The
granular
dorsolateral
prefrontal
cortex
(dlPFC)
is
an
evolutionary
specialization
of
primates
that
centrally
involved
in
cognition.
We
assessed
more
than
600,000
single-nucleus
transcriptomes
from
adult
human,
chimpanzee,
macaque,
and
marmoset
dlPFC.
Although
most
cell
subtypes
defined
transcriptomically
are
conserved,
we
detected
several
exist
only
a
subset
species
as
well
substantial
species-specific
molecular
differences
across
homologous
neuronal,
glial,
non-neural
subtypes.
latter
exemplified
by
human-specific
switching
between
expression
the
neuropeptide
somatostatin
tyrosine
hydroxylase,
rate-limiting
enzyme
dopamine
production
certain
interneurons.
above
also
illustrated
neuropsychiatric
risk
gene
