Life Medicine,
Journal Year:
2024,
Volume and Issue:
3(5)
Published: Oct. 1, 2024
Colorectal
cancer
(CRC),
one
of
the
most
common
tumors
in
world,
is
generally
proposed
to
be
generated
from
intestinal
stem
cells
(ISCs).
Leucine-rich
repeat-containing
G
protein-coupled
receptor
5
(Lgr5)-positive
ISCs
are
located
at
bottom
crypt
and
harbor
self-renewal
differentiation
capacities,
serving
as
resource
all
epithelial
CRC
well.
Here
we
review
recent
progress
both
non-tumoral
tumoral
contexts.
We
summarize
molecular
mechanisms
ISC
self-renewal,
differentiation,
plasticity
for
homeostasis
regeneration.
also
discuss
function
colorectal
tumorigenesis
fate
dynamic,
competition,
niche
regulation,
remote
environmental
regulation
initiation
propagation.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 19, 2024
Perturb-seq
enabled
the
profiling
of
transcriptional
effects
genetic
perturbations
in
single
cells
but
lacks
ability
to
examine
impact
on
tissue
environments.
We
present
Perturb-DBiT
for
simultaneous
co-
sequencing
spatial
transcriptome
and
guide
RNAs
(gRNAs)
same
section
vivo
CRISPR
screen
with
genome-scale
gRNA
libraries,
offering
a
comprehensive
understanding
how
modifications
affect
cellular
behavior
architecture.
This
platform
supports
variety
delivery
vectors,
library
sizes,
preparations,
along
two
distinct
capture
methods,
making
it
adaptable
wide
range
experimental
setups.
In
applying
Perturb-DBiT,
we
conducted
un-biased
knockouts
tens
genes
or
at
genome-wide
scale
across
three
cancer
models.
mapped
all
gRNAs
individual
colonies
corresponding
transcriptomes
human
metastatic
colonization
model,
revealing
clonal
dynamics
cooperation.
also
examined
effect
perturbation
tumor
immune
microenvironment
an
immune-competent
syngeneic
uncovering
differential
synergistic
promoting
infiltration
suppression
tumors.
allows
simultaneously
evaluating
each
knockout
initiation,
development,
metastasis,
histopathology,
landscape.
Ultimately,
not
only
broadens
scope
inquiry,
lays
groundwork
developing
targeted
therapeutic
strategies.
YAKUGAKU ZASSHI,
Journal Year:
2025,
Volume and Issue:
145(2), P. 133 - 143
Published: Jan. 31, 2025
Semaphorins
and
their
receptors
plexins
are
axon
guidance
molecules
that
navigate
axons
to
final
destinations
during
neural
development.
exert
distinct
roles
in
regulating
biological
functions
such
as
the
immune
system
bone
homeostasis.
They
also
participate
development
progression
of
various
diseases
osteoporosis
allergic
diseases.
This
review
describes
varied
phenotypes
revealed
by
analysis
semaphorin
or
plexin
knockout
mice
discusses
association
with
pathogenesis
therapy
atherosclerosis,
agenesis
corpus
callosum,
neuropsychiatric
The
deletion
4D
atherosclerosis-prone
Apolipoprotein
E-deficient
mitigated
atherosclerotic
lesions,
indicating
its
crucial
involvement
atherosclerosis.
Semaphorin
is
implicated
apoptosis
induced
estrogen-dependent
generation
soluble
active
form
plexin-B1
postnatal
vaginal
opening
mice.
Plexin-A1
BALB/cA
exhibited
callosum.
study
indicates
role
plexin-A1
midline
crossing
callosal
pioneer
projecting
from
cerebral
cortex
early
phase
formation.
Adult
plexin-A1-deficient
exhibit
reduced
prepulse
inhibition
deficit,
an
endophenotype
schizophrenia,
addition
excessive
self-grooming.
Parvalbumin-expressing
interneurons
medial
prefrontal
significantly
decreased
In
parvalbumin
neurons,
oxidative
stress
increased
Accordingly,
deficiency
may
augment
thereby
impairing
neuron
network
leading
behavioral
abnormalities
relevant
MedComm,
Journal Year:
2025,
Volume and Issue:
6(3)
Published: Feb. 27, 2025
Abstract
Liver
metastasis
is
a
leading
cause
of
mortality
from
malignant
tumors
and
significantly
impairs
the
efficacy
therapeutic
interventions.
In
recent
years,
both
preclinical
clinical
research
have
made
significant
progress
in
understanding
molecular
mechanisms
strategies
liver
metastasis.
Metastatic
tumor
cells
different
primary
sites
undergo
highly
similar
biological
processes,
ultimately
achieving
ectopic
colonization
growth
liver.
this
review,
we
begin
by
introducing
inherent
metastatic‐friendly
features
We
then
explore
panorama
conclude
three
continuous,
yet
distinct
phases
based
on
liver's
response
to
This
includes
metastatic
sensing
stage,
stress
support
stage.
discuss
intricate
interactions
between
various
resident
recruited
cells.
addition,
emphasize
critical
role
spatial
remodeling
immune
Finally,
review
advancements
challenges
faced
management
Future
precise
antimetastatic
treatments
should
fully
consider
individual
heterogeneity
implement
targeted
interventions
stages
Cell Genomics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 100777 - 100777
Published: Feb. 1, 2025
Genome-wide
CRISPR
screening
in
the
organism
has
tremendous
potential
to
answer
long-standing
questions
of
mammalian
physiology
and
disease.
However,
bringing
this
powerful
technology
vivo
presents
unique
challenges,
including
delivering
a
genome-wide
sgRNA
library
appropriate
cell
type,
achieving
sufficient
coverage
library,
selecting
for
phenotype
interest.
In
review,
we
highlight
recent
advances
delivery,
design,
phenotypic
readout
that
can
help
overcome
these
technical
challenges
thereby
bring
high-throughput
genetic
dissection
an
increasing
number
tissues
questions.
We
are
excited
about
ongoing
innovation
areas
ultimately
enable
any
type
interest
organism,
allowing
unprecedented
investigation
into
diverse
Abstract
Spatially
resolved
in
vivo
CRISPR
screening
integrates
gene
editing
with
spatial
transcriptomics
to
examine
how
genetic
perturbations
alter
expression
within
native
tissue
environments.
However,
current
methods
are
limited
small
perturbation
panels
and
the
detection
of
a
narrow
subset
protein-coding
RNAs.
We
present
Perturb-DBiT,
distinct
versatile
approach
for
simultaneous
co-sequencing
total
RNA
whole-transcriptome
single-guide
RNAs
(sgRNAs),
base-by-base,
on
same
section.
This
method
enables
unbiased
discovery
influence
regulation,
cellular
dynamics,
architecture
situ.
Applying
Perturb-DBiT
human
cancer
metastatic
colonization
model,
we
mapped
large
sgRNAs
across
tumor
colonies
consecutive
sections
alongside
their
corresponding
transcriptomes.
revealed
novel
insights
into
affect
long
non-coding
(lncRNA)
co-variation,
microRNA–mRNA
interactions,
global
tRNA
alterations
amino
acid
metabolism
linked
migration
growth.
By
integrating
transcriptional
pseudotime
trajectories,
further
uncovered
impact
clonal
dynamics
cooperation.
In
an
immune-competent
syngeneic
mouse
enabled
investigation
immune
microenvironment,
revealing
synergistic
effects
infiltration
suppression.
provides
spatially
comprehensive
view
knockouts
diverse
molecular
responses
including
proliferation,
migration,
metastasis,
offering
panoramic
perspective
complex
tissues.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 11, 2024
Reactivated
embryonic
programs
are
associated
with
cancer
progression,
yet
their
role
and
regulatory
mechanisms
remain
poorly
understood.
In
this
study,
we
introduce
‘oncoembryology,’
an
approach
that
systematically
compares
cancerous
tissues
to
identify
shared
molecular
assess
functional
relevance
in
disease.
Applying
strategy
colorectal
cancer,
identified
SoxC
transcription
factors
(Sox4,
Sox11,
Sox12)
as
critical
regulators
of
both
development
tumorigenesis.
regulate
diverse
downstream
targets,
including
Tead2,
Mdk,
Klf4,
thereby
regulating
crucial
steps
colon
development.
Abrogating
function
murine
models
reduced
tumor
growth
prevented
liver
metastasis.
Concordantly,
a
SoxC-driven
oncoembryonic
gene
signature
correlated
poor
survival
patients,
underscoring
the
therapeutic
potential
targeting
SoxC-regulated
pathways
treatment.
