bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Май 10, 2023
ABSTRACT
Cells
live
and
interact
in
three-dimensional
(3D)
cellular
neighborhoods.
However,
histology
spatial
omics
methods
mostly
focus
on
2D
tissue
sections.
Here
we
present
a
3D
atlas
of
routine
clinical
sample,
an
aggressive
human
lung
carcinoma,
by
combining
situ
quantification
960
cancer-related
genes
across
∼340,000
cells
with
measurements
tissue-mechanical
components.
neighborhoods
subdivided
the
tumor
microenvironment
into
tumor,
stromal,
immune
multicellular
niches.
Interestingly,
pseudotime
analysis
suggested
that
pro-invasive
epithelial-to-mesenchymal
transition
(EMT),
detected
stroma-infiltrating
cells,
already
occurred
one
region
at
surface.
There,
myofibroblasts
macrophages
specifically
co-localized
pre-invasive
their
molecular
signature
identified
patients
shorter
survival.
Moreover,
cytotoxic
T-cells
did
not
infiltrate
this
niche
but
colocalized
inhibitory
dendritic
regulatory
T
cells.
Importantly,
systematic
scoring
cell-cell
interactions
highlighted
niche-specific
signaling
networks
accompanying
invasion
escape.
Compared
to
2D,
improved
characterization
niches
identifying
niches,
capturing
extension
T-cell
boosting
interactions,
including
druggable
checkpoints.
We
believe
communication
analyses
can
improve
design
studies
investigating
personalized,
combination
immuno-oncology
therapies.
Nature Biotechnology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
Efficient
and
accurate
nanocarrier
development
for
targeted
drug
delivery
is
hindered
by
a
lack
of
methods
to
analyze
its
cell-level
biodistribution
across
whole
organisms.
Here
we
present
Single
Cell
Precision
Nanocarrier
Identification
(SCP-Nano),
an
integrated
experimental
deep
learning
pipeline
comprehensively
quantify
the
targeting
nanocarriers
throughout
mouse
body
at
single-cell
resolution.
SCP-Nano
reveals
tissue
distribution
patterns
lipid
nanoparticles
(LNPs)
after
different
injection
routes
doses
as
low
0.0005
mg
kg-1-far
below
detection
limits
conventional
imaging
techniques.
We
demonstrate
that
intramuscularly
injected
LNPs
carrying
SARS-CoV-2
spike
mRNA
reach
heart
tissue,
leading
proteome
changes,
suggesting
immune
activation
blood
vessel
damage.
generalizes
various
types
nanocarriers,
including
liposomes,
polyplexes,
DNA
origami
adeno-associated
viruses
(AAVs),
revealing
AAV2
variant
transduces
adipocytes
body.
enables
comprehensive
three-dimensional
mapping
bodies
with
high
sensitivity
should
accelerate
precise
safe
nanocarrier-based
therapeutics.
Molecular Systems Biology,
Год журнала:
2023,
Номер
19(11)
Опубликована: Окт. 16, 2023
Abstract
Spatial
omics
has
emerged
as
a
rapidly
growing
and
fruitful
field
with
hundreds
of
publications
presenting
novel
methods
for
obtaining
spatially
resolved
information
any
data
type
on
spatial
scales
ranging
from
subcellular
to
organismal.
From
technology
development
perspective,
is
highly
interdisciplinary
that
integrates
imaging
omics,
molecular
analyses,
sequencing
mass
spectrometry,
image
analysis
bioinformatics.
The
emergence
this
not
only
opened
window
into
biology,
but
also
created
multiple
opportunities,
questions,
challenges
method
developers.
Here,
we
provide
the
perspective
developers
what
makes
unique.
After
providing
brief
overview
state
art,
discuss
technological
enablers
present
our
vision
about
future
applications
impact
melting
pot.
Circulation Research,
Год журнала:
2024,
Номер
134(11), С. 1546 - 1565
Опубликована: Май 23, 2024
Cardiac
abnormalities
were
identified
early
in
the
epidemic
of
AIDS,
predating
isolation
and
characterization
etiologic
agent,
HIV.
Several
decades
later,
causation
pathogenesis
cardiovascular
disease
(CVD)
linked
to
HIV
infection
continue
be
focus
intense
speculation.
Before
widespread
use
antiretroviral
therapy,
HIV-associated
CVD
was
primarily
characterized
by
cardiomyopathy
profound
immunodeficiency.
With
increasing
therapy
use,
viral
load
suppression,
establishment
immune
competency,
effects
on
system
are
more
subtle.
Yet,
people
living
with
still
face
an
increased
incidence
pathology.
Advances
cardiac
imaging
modalities
immunology
have
deepened
our
understanding
CVD.
This
review
provides
overview
integrating
data
from
immunologic
studies
particular
relevance
population
originating
high-endemic
regions,
such
as
sub-Saharan
Africa.
The
highlights
key
evidence
gaps
field
suggests
future
directions
for
research
better
understand
complex
HIV-CVD
interactions.
Substantial
efforts
are
underway
to
deepen
our
understanding
of
human
brain
morphology,
structure,
and
function
using
high-resolution
imaging
as
well
high-content
molecular
profiling
technologies.
The
current
work
adds
these
approaches
by
providing
a
comprehensive
quantitative
protein
expression
map
13
anatomically
distinct
regions
covering
more
than
11,000
proteins.
This
was
enabled
the
optimization,
characterization,
implementation
high-sensitivity
high-throughput
microflow
liquid
chromatography
timsTOF
tandem
mass
spectrometry
system
(LC-MS/MS)
capable
analyzing
2,000
consecutive
samples
prepared
from
formalin-fixed
paraffin
embedded
(FFPE)
material.
Analysis
this
proteomic
resource
highlighted
region-enriched
patterns
functional
classes,
localization
differences
between
individual
markers
for
specific
areas.
To
facilitate
access
ease
further
mining
data
scientific
community,
all
can
be
explored
online
in
purpose-built
R
Shiny
app
(https://brain-region-atlas.proteomics.ls.tum.de).
Nature Biotechnology,
Год журнала:
2023,
Номер
41(12), С. 1734 - 1745
Опубликована: Апрель 17, 2023
Abstract
While
genetically
encoded
reporters
are
common
for
fluorescence
microscopy,
equivalent
multiplexable
gene
electron
microscopy
(EM)
still
scarce.
Here,
by
installing
a
variable
number
of
fixation-stable
metal-interacting
moieties
in
the
lumen
encapsulin
nanocompartments
different
sizes,
we
developed
suite
spherically
symmetric
and
concentric
barcodes
(EMcapsulins)
that
readable
standard
EM
techniques.
Six
classes
EMcapsulins
could
be
automatically
segmented
differentiated.
The
coding
capacity
was
further
increased
arranging
several
into
distinct
patterns
via
set
rigid
spacers
length.
Fluorescent
were
expressed
to
monitor
subcellular
structures
light
EM.
Neuronal
expression
Drosophila
mouse
brains
enabled
automatic
identification
defined
cells
compatible
with
transmission
EM,
scanning
focused
ion
beam
expandable
palette
controlled
EM-readable
can
augment
anatomical
images
multiplexed
maps.
Clinical and Translational Medicine,
Год журнала:
2025,
Номер
15(4)
Опубликована: Март 28, 2025
Abstract
Atherosclerosis
is
a
chronic
inflammatory
condition
of
the
arteries,
marked
by
development
plaques
within
arterial
intima.
The
rupture
unstable
can
lead
to
thrombosis,
downstream
vessel
occlusion
and
serious
clinical
events.
composition
atherosclerotic
complex
highly
heterogeneous,
posing
challenges
for
their
study.
current
pathology
histological
subtype
classification
may
fail
fully
encompass
microscopic
molecular
components
in
tissue,
disease
progress
various
stages
atherosclerosis
potential
mechanism
plaque
rupture.
However,
spatial
mapping
heterogeneity
tissue
enhance
our
understanding
these
lesions.
Despite
considerable
made
traditional
omics
field
research,
its
status
as
an
indispensable
technology,
there
remain
inherent
limitations
investigation
minute
molecular.
In
recent
years,
techniques
have
advanced
significantly,
enabling
visualisation
analysis
specific
that
serve
causal
targets
associated
with
progression.
effective
application
both
research
settings
represents
promising
area
further
exploration.
This
review
focuses
on
advancements
findings
related
study
extracranial
carotid
cerebrovascular
disease.
Spatial
facilitate
detection
biomarkers
diagnostic
significance
or
relevance
disease,
offering
new
methods
insights
into
diagnosis
complications.
Journal of Proteome Research,
Год журнала:
2024,
Номер
23(8), С. 2700 - 2722
Опубликована: Март 7, 2024
The
mammalian
cell
is
a
complex
entity,
with
membrane-bound
and
membrane-less
organelles
playing
vital
roles
in
regulating
cellular
homeostasis.
Organellar
protein
niches
drive
discrete
biological
processes
functions,
thus
maintaining
equilibrium.
Cellular
such
as
signaling,
growth,
proliferation,
motility,
programmed
death
require
dynamic
movements
between
compartments.
Aberrant
localization
associated
wide
range
of
diseases.
Therefore,
analyzing
the
subcellular
proteome
can
provide
comprehensive
overview
biology.
With
recent
advancements
mass
spectrometry,
imaging
technology,
computational
tools,
deep
machine
learning
algorithms,
studies
pertaining
to
their
distributions
are
gaining
momentum.
These
reveal
changing
interaction
networks
because
"moonlighting
proteins"
serve
discovery
tool
for
disease
network
mechanisms.
Consequently,
this
review
aims
repository
proteomics
subcontexting
methods,
challenges,
future
perspectives
method
developers.
In
summary,
crucial
understanding
fundamental
mechanisms
Frontiers in Medical Technology,
Год журнала:
2024,
Номер
6
Опубликована: Сен. 9, 2024
When
faced
with
the
prospect
of
death,
some
people
would
prefer
a
form
long-term
preservation
that
may
allow
them
to
be
restored
healthy
life
in
future,
if
technology
ever
develops
point
this
is
feasible
and
humane.
Some
believe
we
have
capacity
perform
type
experimental
today-although
it
has
never
been
proven-using
contemporary
methods
preserve
structure
brain.
The
idea
morphomolecular
organization
brain
encodes
information
required
for
psychological
properties
such
as
personality
memories.
If
these
structures
can
maintained
intact
over
time,
could
theoretically
provide
bridge
access
restorative
technologies
future.
To
consider
hypothesis,
first
describe
possible
metrics
used
assess
structural
quality.
We
next
explore
several
brain,
including
traditional
cryonics
method
cryopreservation,
well
aldehyde-stabilized
cryopreservation
fluid
preservation.
focus
in-depth
on
preservation,
which
relies
aldehyde
fixation
induce
chemical
gel
formation
wide
set
biomolecules
appears
cost-effective
method.
two
theoretical
recovery
technologies,
alongside
ethical
legal
complexities
all
will
require
prudent
approach.
non-negligible
chance
allowing
successful
restoration
future
deserves
serious
research
efforts
by
scientific
community.
