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.
Cell,
Год журнала:
2023,
Номер
186(2), С. 363 - 381.e19
Опубликована: Янв. 1, 2023
Advanced
solid
cancers
are
complex
assemblies
of
tumor,
immune,
and
stromal
cells
characterized
by
high
intratumoral
variation.
We
use
highly
multiplexed
tissue
imaging,
3D
reconstruction,
spatial
statistics,
machine
learning
to
identify
cell
types
states
underlying
morphological
features
known
diagnostic
prognostic
significance
in
colorectal
cancer.
Quantitation
these
high-plex
marker
space
reveals
recurrent
transitions
from
one
tumor
morphology
the
next,
some
which
coincident
with
long-range
gradients
expression
oncogenes
epigenetic
regulators.
At
invasive
margin,
where
normal,
immune
compete,
T
suppression
involves
multiple
imaging
shows
that
seemingly
localized
2D
such
as
tertiary
lymphoid
structures
commonly
interconnected
have
graded
molecular
properties.
Thus,
while
cancer
genetics
emphasizes
importance
discrete
changes
state,
whole-specimen
large-scale
analogous
those
developing
tissues.
Nature Methods,
Год журнала:
2021,
Номер
19(3), С. 311 - 315
Опубликована: Ноя. 25, 2021
Highly
multiplexed
tissue
imaging
makes
detailed
molecular
analysis
of
single
cells
possible
in
a
preserved
spatial
context.
However,
reproducible
large
multichannel
images
poses
substantial
computational
challenge.
Here,
we
describe
modular
and
open-source
pipeline,
MCMICRO,
for
performing
the
sequential
steps
needed
to
transform
whole-slide
into
single-cell
data.
We
demonstrate
use
MCMICRO
on
tumor
acquired
using
multiple
platforms,
thereby
providing
solid
foundation
continued
development
software.
Nature Methods,
Год журнала:
2023,
Номер
20(10), С. 1530 - 1536
Опубликована: Окт. 1, 2023
Single-cell
proteomics
by
mass
spectrometry
is
emerging
as
a
powerful
and
unbiased
method
for
the
characterization
of
biological
heterogeneity.
So
far,
it
has
been
limited
to
cultured
cells,
whereas
an
expansion
complex
tissues
would
greatly
enhance
insights.
Here
we
describe
single-cell
Deep
Visual
Proteomics
(scDVP),
technology
that
integrates
high-content
imaging,
laser
microdissection
multiplexed
spectrometry.
scDVP
resolves
context-dependent,
spatial
proteome
murine
hepatocytes
at
current
depth
1,700
proteins
from
cell
slice.
Half
was
differentially
regulated
in
manner,
with
protein
levels
changing
dramatically
proximity
central
vein.
We
applied
machine
learning
classes
images,
which
subsequently
inferred
imaging
data
alone.
applicable
healthy
diseased
complements
other
omics
technologies.
Nature Cancer,
Год журнала:
2023,
Номер
4(7), С. 1036 - 1052
Опубликована: Июнь 22, 2023
Precision
medicine
is
critically
dependent
on
better
methods
for
diagnosing
and
staging
disease
predicting
drug
response.
Histopathology
using
hematoxylin
eosin
(H&E)-stained
tissue
(not
genomics)
remains
the
primary
diagnostic
method
in
cancer.
Recently
developed
highly
multiplexed
imaging
promise
to
enhance
research
studies
clinical
practice
with
precise,
spatially
resolved
single-cell
data.
Here,
we
describe
'Orion'
platform
collecting
H&E
high-plex
immunofluorescence
images
from
same
cells
a
whole-slide
format
suitable
diagnosis.
Using
retrospective
cohort
of
74
colorectal
cancer
resections,
show
that
provide
human
experts
machine
learning
algorithms
complementary
information
can
be
used
generate
interpretable,
image-based
models
predictive
progression-free
survival.
Combining
immune
infiltration
tumor-intrinsic
features
achieves
10-
20-fold
discrimination
between
rapid
slow
(or
no)
progression,
demonstrating
ability
multimodal
high-performance
biomarkers.
The
amniote
pallium
contains
sensory
circuits
that
are
structurally
and
functionally
equivalent,
yet
their
evolutionary
relationship
remains
unresolved.
We
used
birthdating
analysis,
single-cell
RNA
spatial
transcriptomics,
mathematical
modeling
to
compare
the
development
evolution
of
known
pallial
across
birds
(chick),
lizards
(gecko),
mammals
(mouse).
reveal
neurons
within
these
circuits’
stations
generated
at
varying
developmental
times
brain
regions
species
found
an
early
divergence
in
transcriptomic
progression
glutamatergic
neurons.
Our
research
highlights
distinctions
functional
similarities
circuit
between
mammals,
suggesting
convergence
high-order
processing
lineages.
