Abstract
Reliable
methods
for
detecting
and
analyzing
gene
expression
are
necessary
tools
understanding
development
investigating
biological
responses
to
genetic
environmental
perturbation.
With
its
fully
sequenced
genome,
invariant
cell
lineage,
transparent
body,
wiring
diagram,
detailed
anatomy,
wide
array
of
tools,
Caenorhabditis
elegans
is
an
exceptionally
useful
model
organism
linking
cellular
phenotypes.
The
new
techniques
in
recent
years
has
greatly
expanded
our
ability
detect
at
high
resolution.
Here,
we
provide
overview
C.
elegans,
including
transcripts
proteins
situ,
bulk
RNA
sequencing
whole
worms
specific
tissues
cells,
single-cell
sequencing,
high-throughput
proteomics.
We
discuss
important
considerations
choosing
among
these
publicly
available
online
resources
data.
Aging
is
characterized
by
a
decline
in
tissue
function,
but
the
underlying
changes
at
cellular
resolution
across
organism
remain
unclear.
Here,
we
present
Fly
Cell
Atlas,
single-nucleus
transcriptomic
map
of
whole
aging
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Фев. 21, 2025
Normal
aging
alters
brain
functions
and
phenotypes.
However,
it
is
not
well
understood
how
astrocytes
are
impacted
by
aging,
nor
they
contribute
to
neuronal
dysfunction
disease
risk
as
organisms
age.
Here,
we
examine
the
transcriptional,
cell
biology,
functional
differences
in
across
normal
aging.
Astrocytes
at
baseline
heterogenous,
responsive
their
environments,
critical
regulators
of
microenvironments
function.
With
increasing
age,
adopt
different
immune-related
senescence-associated
states,
which
relate
organelle
loss
homeostasis
maintenance,
both
autonomously
non-cell
autonomously.
These
perturbed
states
increasingly
associated
with
age-related
onset
neurodegeneration,
suggesting
that
astrocyte
a
compelling
target
for
future
manipulation
prevention
disease.
Cognitive
decline
is
a
significant
health
concern
in
our
aging
society.
Here,
we
used
the
model
organism
C.
elegans
to
investigate
impact
of
IIS/FOXO
pathway
on
age-related
cognitive
decline.
The
daf-2
Insulin/IGF-1
receptor
mutant
exhibits
extension
learning
and
memory
span
with
age
compared
wild-type
worms,
an
effect
that
dependent
DAF-16
transcription
factor.
To
identify
possible
mechanisms
by
which
mutants
maintain
while
worms
lose
neuronal
function,
carried
out
neuron-specific
transcriptomic
analysis
aged
animals.
We
observed
downregulation
genes
upregulation
transcriptional
regulation
neurons.
By
contrast,
exhibit
distinct
alterations
response
aging,
including
stress
specific
insulin
signaling
genes.
tested
roles
significantly
transcriptionally-changed
regulating
functions,
identifying
novel
regulators
memory.
In
addition
other
mechanistic
insights,
comparison
vs
young
transcriptome
revealed
new
set
potentially
neuroprotective
upregulated;
instead
simply
mimicking
state,
may
enhance
resilience
accumulation
harm
take
more
active
approach
combat
aging.
These
findings
suggest
potential
mechanism
for
function
offer
insights
into
therapeutic
targets
To
elucidate
aging-associated
cellular
population
dynamics,
we
present
PanSci
,
a
single-cell
transcriptome
atlas
profiling
over
20
million
cells
from
623
mouse
tissues
across
different
life
stages,
sexes,
and
genotypes.
This
comprehensive
dataset
reveals
more
than
3,000
unique
states
200
cell
populations.
Our
panoramic
analysis
uncovered
organ-,
lineage-,
sex-specific
shifts
of
dynamics
during
lifespan
progression.
Moreover,
identify
both
systematic
organ-specific
alterations
in
immune
populations
associated
with
aging.
We
further
explored
the
regulatory
roles
system
on
aging
pinpointed
specific
age-related
expansions
that
are
lymphocyte
dependent.
“cell-omics”
strategy
enhances
comprehension
lays
groundwork
for
exploring
complex
networks
diseases.
Abstract
This
book
chapter
will
focus
on
modifications
to
chromatin
itself,
how
are
regulated,
and
these
deciphered
by
the
cell
impact
aging.
In
this
chapter,
we
review
change
with
age,
examine
chromatin-modifying
enzymes
have
been
shown
regulate
aging
healthspan,
discuss
some
of
epigenetic
changes
triggered
they
can
lifespan
individual
its
naïve
descendants,
speculate
future
directions
for
field.
In
eukaryotic
cells,
lipid
transfer
can
occur
at
membrane
contact
sites
(MCS)
to
facilitate
the
exchange
of
various
lipids
between
two
adjacent
cellular
organelle
membranes.
Lipid
proteins
(LTPs),
including
shuttle
LTP
or
bridge-like
(BLTP),
transport
MCS
and
are
critical
for
diverse
processes,
metabolism,
trafficking,
cell
signaling.
BLTPs
(BLTP1-5,
ATG2
VPS13
family
proteins)
contain
lipid-accommodating
hydrophobic
repeating
β-groove
(RBG)
domains
that
allow
bulk
through
MCS.
Compared
with
vesicular
LTP,
have
been
only
recently
identified.
Their
functions
regulatory
mechanisms
currently
being
unraveled
in
model
organisms
by
approaches.
this
review,
we
summarize
genetics,
structural
features,
biological
BLTP
genetically
tractable
organism
C.
elegans.
We
discuss
our
recent
studies
findings
on
elegans
LPD-3,
a
prototypical
megaprotein
ortholog
BLTP1,
identified
evolutionarily
conserved
multicellular
human
cells.
also
highlight
areas
future
research
using
complementary
systems
Given
emerging
links
several
diseases,
Parkinson's
disease
Alkuraya-Kučinskas
syndrome,
discovering
roles
their
regulation
action
should
contribute
new
advances
basic
biology
potential
therapeutic
development
related
disorders.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 26, 2024
ABSTRACT
Protein
clearance
is
fundamental
to
proteome
health.
In
eukaryotes,
it
carried
by
two
highly
conserved
proteolytic
systems,
the
ubiquitin-proteasome
system
(UPS)
and
autophagy-lysosome
pathway
(ALP).
Despite
their
pivotal
role,
basal
organization
of
human
protein
systems
across
tissues
cell
types
remains
uncharacterized.
Here,
we
interrogated
this
using
diverse
omics
datasets.
Relative
other
protein-coding
genes,
UPS
ALP
genes
were
more
widely
expressed,
encoded
housekeeping
proteins,
essential
for
growth,
in
accordance
with
roles.
Most
nevertheless
differentially
expressed
tissues,
tissue-specific
upregulation
was
associated
functions,
phenotypes,
disease
susceptibility.
The
small
subset
that
stably
growth
than
suggesting
acts
as
a
core.
Lastly,
compared
branches
proteostasis
network.
folding
closely
coordinated
yet
both
less
synthesis.
Taken
together,
propose
network
organized
hierarchically
tailored
needs.
This
could
contribute
illuminate
tissue-selective
phenotypes.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 16, 2024
Abstract
Metabolism
is
fundamental
to
organism
physiology
and
pathology.
From
the
intricate
network
of
metabolic
reactions,
diverse
chemical
molecules,
collectively
termed
as
metabolites,
are
produced.
In
multicellular
organisms,
metabolite
communication
between
different
tissues
vital
for
maintaining
homeostasis
adaptation.
However,
molecular
mechanisms
mediating
these
communications
remain
poorly
understood.
Here,
we
focus
on
nucleosides
nucleotides,
essential
metabolites
involved
in
multiple
cellular
processes,
report
pivotal
role
SLC29A
family
transporters
nucleoside
coordination
soma
germline.
Through
genetic
analysis,
discovered
that
two
Caenorhabditis
elegans
homologs
transporters,
Equilibrative
Nucleoside
Transporter
ENT-1
ENT-2,
act
germline
intestine,
respectively,
regulate
reproduction.
Their
knockdown
synergistically
results
sterility.
Further
single-cell
transcriptomic
targeted
metabolomic
profiling
revealed
ENT
double
specifically
affects
genes
purine
biosynthesis
pathway
reduces
ratio
guanosine
adenosine
levels.
Importantly,
supplementation
into
body
cavity/pseudocoelom
through
microinjection
rescued
sterility
caused
by
knockdown,
whereas
had
no
effect.
Together,
studies
support
a
rate
limiting
factor
control
reproduction,
uncover
previously
unknown
nucleoside/nucleotide
reproductive
success,
highlight
significance
SLC-mediated
cell-nonautonomous
regulating
physiology.
Author
Summary
life,
involving
complex
reactions
requires
well-organized
system
maintain
efficiency.
This
includes
optimal
allocation
resources
dynamic
exchange
products
various
compartments
within
an
organism.
Solute
carriers
(SLCs)
largest
across
animal
kingdom.
our
research,
investigated
how
specific
SLC
collaborate
move
key
tissues.
We
identified
which
transporting
guanosine,
nucleoside,
successful
reproduction
nematode
.
ENT-2
acts
gut
export
surrounding
cavity,
while
functions
import
from
cavity.
When
both
disrupted,
animals
experience
significant
defects.
Our
study
underscores
importance
coordinated
activity
health.
A
breakdown
this
can
result
imbalances
physiological
dysfunction.
