Molecular Cell,
Journal Year:
2023,
Volume and Issue:
83(9), P. 1446 - 1461.e6
Published: March 29, 2023
Summary
Enhancer
clusters
overlapping
disease-associated
mutations
in
Pierre
Robin
sequence
(PRS)
patients
regulate
SOX9
expression
at
genomic
distances
over
1.25
Mb.
We
applied
optical
reconstruction
of
chromatin
architecture
(ORCA)
imaging
to
trace
3D
locus
topology
during
PRS-enhancer
activation.
observed
pronounced
changes
between
cell
types.
Subsequent
analysis
single-chromatin
fiber
traces
revealed
that
these
ensemble-average
differences
arise
through
the
frequency
commonly
sampled
topologies.
further
identified
two
CTCF-bound
elements,
internal
topologically
associating
domain,
which
promote
stripe
formation,
are
positioned
near
domain's
geometric
center,
and
bridge
enhancer-promoter
contacts
a
series
loops.
Ablation
elements
results
diminished
altered
domain-wide
contacts.
Polymer
models
with
uniform
loading
across
domain
frequent
cohesin
collisions
recapitulate
this
multi-loop,
centrally
clustered
geometry.
Together,
we
provide
mechanistic
insights
into
architectural
formation
gene
regulation
ultra-long
ranges.
Genome Medicine,
Journal Year:
2022,
Volume and Issue:
14(1)
Published: June 27, 2022
Abstract
Single-cell
transcriptomics
(scRNA-seq)
has
become
essential
for
biomedical
research
over
the
past
decade,
particularly
in
developmental
biology,
cancer,
immunology,
and
neuroscience.
Most
commercially
available
scRNA-seq
protocols
require
cells
to
be
recovered
intact
viable
from
tissue.
This
precluded
many
cell
types
study
largely
destroys
spatial
context
that
could
otherwise
inform
analyses
of
identity
function.
An
increasing
number
platforms
now
facilitate
spatially
resolved,
high-dimensional
assessment
gene
transcription,
known
as
‘spatial
transcriptomics’.
Here,
we
introduce
different
classes
method,
which
either
record
locations
hybridized
mRNA
molecules
tissue,
image
positions
themselves
prior
assessment,
or
employ
arrays
probes
pre-determined
location.
We
review
sizes
tissue
area
can
assessed,
their
resolution,
genes
profiled.
discuss
if
preservation
influences
choice
platform,
provide
guidance
on
whether
specific
may
better
suited
discovery
screens
hypothesis
testing.
Finally,
bioinformatic
methods
analysing
transcriptomic
data,
including
pre-processing,
integration
with
existing
inference
cell-cell
interactions.
Spatial
-omics
are
already
improving
our
understanding
human
tissues
research,
diagnostic,
therapeutic
settings.
To
build
upon
these
recent
advancements,
entry-level
those
seeking
own
research.
Science,
Journal Year:
2023,
Volume and Issue:
381(6657)
Published: Aug. 3, 2023
Spatial
omics
has
been
widely
heralded
as
the
new
frontier
in
life
sciences.
This
term
encompasses
a
wide
range
of
techniques
that
promise
to
transform
many
areas
biology
and
eventually
revolutionize
pathology
by
measuring
physical
tissue
structure
molecular
characteristics
at
same
time.
Although
field
came
age
past
5
years,
it
still
suffers
from
some
growing
pains:
barriers
entry,
robustness,
unclear
best
practices
for
experimental
design
analysis,
lack
standardization.
In
this
Review,
we
present
systematic
catalog
different
families
spatial
technologies;
highlight
their
principles,
power,
limitations;
give
perspective
suggestions
on
biggest
challenges
lay
ahead
incredibly
powerful-but
hard
navigate-landscape.
Science,
Journal Year:
2021,
Volume and Issue:
373(6556)
Published: Aug. 12, 2021
Capturing
the
heterogeneous
phenotypes
of
microbial
populations
at
relevant
spatiotemporal
scales
is
highly
challenging.
Here,
we
present
par-seqFISH
(parallel
sequential
fluorescence
in
situ
hybridization),
a
transcriptome-imaging
approach
that
records
gene
expression
and
spatial
context
within
microscale
assemblies
single-cell
molecule
resolution.
We
applied
this
to
opportunistic
pathogen
Pseudomonas
aeruginosa,
analyzing
about
600,000
individuals
across
dozens
conditions
planktonic
biofilm
cultures.
identified
numerous
metabolic-
virulence-related
transcriptional
states
emerged
dynamically
during
growth,
as
well
spatially
resolved
metabolic
heterogeneity
sessile
populations.
Our
data
reveal
distinct
physiological
can
coexist
same
just
several
micrometers
away,
underscoring
importance
microenvironment.
results
illustrate
complex
dynamics
new
way
studying
them
high
Nature,
Journal Year:
2023,
Volume and Issue:
616(7955), P. 113 - 122
Published: March 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.