bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Abstract
In
vitro
human
organoid
models
have
become
transformative
tools
for
studying
organogenesis,
enabling
the
generation
of
spinal
cord
organoids
(SCOs)
that
mimic
aspects
biology.
However,
current
do
not
produce
motor
neurons
(spMNs)
with
a
wide
range
axial
identities
along
segments
within
single
structure,
limiting
their
utility
in
understanding
neural
specification
and
selective
vulnerability
spMN
subpopulations
neuron
diseases.
Here,
we
present
novel
approach
to
enhance
heterogeneity
an
advanced
SCO
model
derived
from
stem
cells
(NSCs)
retinoic
acid
(RA)-primed
neuromesodermal
progenitors
(NMPs).
RA
priming
guided
NMP
differentiation
into
caudal
progenitors,
generating
SCOs
enriched
spMNs
posterior
identities.
To
further
diversify
populations,
optimized
by
synchronously
patterning
NSCs
RA-primed
NMPs.
Incorporating
endothelial-like
network
skeletal
muscle
enhanced
organoids’
physiological
complexity
maturation
cell
viability.
This
comprehensive
approach,
termed
CASCO,
provides
robust
platform
study
neurodegenerative
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 10, 2024
Recent
dynamic
lineage
tracing
technologies
combine
CRISPR-based
genome
editing
with
single-cell
sequencing
to
track
cell
divisions
during
development.
A
key
computational
problem
in
is
infer
a
tree
from
the
measured
CRISPR-induced
mutations.
Three
features
of
data
distinguish
this
standard
phylogenetic
inference.
First,
CRISPR-editing
process
modifies
genomic
location
exactly
once.
This
Nature Reviews Genetics,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 25, 2024
A
paradigm
for
biology
is
emerging
in
which
cells
can
be
genetically
programmed
to
write
their
histories
into
own
genomes.
These
records
subsequently
read,
and
the
cellular
reconstructed,
each
cell
could
include
a
record
of
its
lineage
relationships,
extrinsic
influences,
internal
states
physical
locations,
over
time.
DNA
recording
has
potential
transform
way
that
we
study
developmental
disease
processes.
Recent
advances
genome
engineering
are
driving
development
systems
recording,
meanwhile
single-cell
spatial
omics
technologies
increasingly
enable
recovery
recorded
information.
Combined
with
computational
phylogenetic
inference
algorithms,
beginning
bear
fruit.
In
this
Perspective,
explore
rationale
technical
basis
what
aspects
might
how,
types
discovery
anticipate
will
enable.
Organoids
and
stem-cell-based
embryo
models
(SEMs)
are
imperfect
organ
or
representations
that
explore
a
much
larger
space
of
possible
forms,
morphospace,
compared
to
their
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 10, 2024
Abstract
Developmental
genes
are
controlled
by
an
ensemble
of
cis
-acting
regulatory
elements
(REs),
which
in
turn
respond
to
multiple
trans
transcription
factors
(TFs).
Understanding
how
a
-regulatory
landscape
integrates
information
from
many
dynamically
expressed
TFs
has
remained
challenge.
We
develop
combined
CRISPR-screening
approach
using
endogenous
RNA
and
RE-reporters
as
readouts.
Applied
the
Xist
locus,
crucial
for
X-chromosome
inactivation
females,
this
method
allows
us
comprehensively
identify
Xist-controlling
map
their
TF-RE
wiring.
find
group
transiently
that
regulate
proximal
REs,
driving
binary
activation
expression.
These
basal
activators
more
highly
cells
with
two
X
chromosomes,
potentially
female-specific
upregulation.
A
second
set
developmental
is
upregulated
later
during
differentiation
targets
distal
REs.
This
axis
achieve
high
levels
RNA,
necessary
inactivation.
Our
findings
support
model
gene
regulation
targeting
REs
drive
ON-OFF
decisions,
while
interacting
control
output.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Abstract
In
vitro
human
organoid
models
have
become
transformative
tools
for
studying
organogenesis,
enabling
the
generation
of
spinal
cord
organoids
(SCOs)
that
mimic
aspects
biology.
However,
current
do
not
produce
motor
neurons
(spMNs)
with
a
wide
range
axial
identities
along
segments
within
single
structure,
limiting
their
utility
in
understanding
neural
specification
and
selective
vulnerability
spMN
subpopulations
neuron
diseases.
Here,
we
present
novel
approach
to
enhance
heterogeneity
an
advanced
SCO
model
derived
from
stem
cells
(NSCs)
retinoic
acid
(RA)-primed
neuromesodermal
progenitors
(NMPs).
RA
priming
guided
NMP
differentiation
into
caudal
progenitors,
generating
SCOs
enriched
spMNs
posterior
identities.
To
further
diversify
populations,
optimized
by
synchronously
patterning
NSCs
RA-primed
NMPs.
Incorporating
endothelial-like
network
skeletal
muscle
enhanced
organoids’
physiological
complexity
maturation
cell
viability.
This
comprehensive
approach,
termed
CASCO,
provides
robust
platform
study
neurodegenerative
