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
Considerable
phenotypic
variation
under
identical
culture
conditions
limits
the
potential
of
stem-cell-based
embryo
models
(SEMs)
in
basic
and
applied
research.
The
biological
processes
causing
this
seemingly
stochastic
remain
unclear.
Here,
we
investigated
roots
by
parallel
recording
transcriptomic
states
morphological
history
individual
structures
modeling
embryonic
trunk
formation.
Machine
learning
integration
time-resolved
single-cell
RNA
sequencing
with
imaging-based
profiling
identified
early
features
predictive
end
states.
Leveraging
power
revealed
that
imbalance
oxidative
phosphorylation
glycolysis
results
aberrant
morphology
a
neural
lineage
bias,
which
confirmed
metabolic
measurements.
Accordingly,
interventions
improved
Collectively,
our
work
establishes
divergent
as
drivers
offers
broadly
applicable
framework
to
chart
predict
organoids
SEMs.
strategy
can
be
used
identify
control
underlying
processes,
ultimately
increasing
reproducibility.
ABSTRACT
Pluripotency,
the
capacity
to
generate
all
cells
of
body,
is
a
defining
property
transient
population
epiblast
found
in
pre-,
peri-
and
post-implantation
mammalian
embryos.
As
development
progresses,
undergo
dynamic
transitions
pluripotency
states,
concurrent
with
specification
extra-embryonic
embryonic
lineages.
Recently,
stem
cell-based
models
pre-
human
have
been
developed
using
that
capture
key
properties
at
different
developmental
stages.
Here,
we
review
early
primate
development,
comparing
states
vivo
cultured
pluripotent
representative
these
states.
We
consider
how
status
starting
influences
embryo
and,
turn,
what
can
learn
about
epiblast.
Finally,
discuss
limitations
questions
arising
from
pioneering
studies
this
emerging
field.
Abstract
Gastrulation
is
a
key
milestone
in
the
development
of
an
organism.
It
period
cell
proliferation
and
coordinated
cellular
rearrangement,
that
creates
outline
body
plan.
Our
current
understanding
mammalian
gastrulation
has
been
improved
by
embryo
culture,
but
there
are
still
many
open
questions
difficult
to
address
because
intrauterine
embryos
low
number
specimens.
In
case
humans,
additional
difficulties
associated
with
technical
ethical
challenges.
Over
last
few
years,
pluripotent
stem
models
being
developed
have
potential
become
useful
tools
understand
gastrulation.
Here
we
review
these
special
emphasis
on
gastruloids
provide
survey
methods
produce
them
robustly,
their
uses,
relationship
embryos,
prospects
as
well
limitations.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 13, 2024
During
development,
mulitpotent
cells
differentiate
through
a
hierarchy
of
increasingly
restricted
progenitor
cell
types
until
they
realize
specialized
types.
A
differentiation
map
describes
this
hierarchy,
and
inferring
these
maps
is
an
active
area
research
spanning
traditional
single
marker
lineage
studies
to
data-driven
trajectory
inference
methods
on
single-cell
RNA-seq
data.
Recent
high-throughput
tracing
technologies
profile
lineages
at
scale,
but
current
infer
from
data
rely
simple
models
with
restrictive
assumptions
about
the
developmental
process.
We
introduce
mathematical
framework
for
based
concept
potency,
develop
algorithm,
Zebrafish
(Danio
rerio)
is
an
important
developmental
biology
and
genetic
animal
model.
Its
educational
use
provides
students
with
the
opportunity
for
research-based
learning,
leading
to
high-quality
integration
of
theoretical
knowledge
practical
skills.
In
this
study,
we
explored
a
didactic
approach
teaching
using
zebrafish.
We
describe
curriculum
design
course
workflow
based
on
several
pedagogical
strategies
tools
that
facilitate
effectiveness.
Students'
opinions
confirm
accessible
during
laboratories
lectures.
Moreover,
observed
increasing
number
willing
perform
research
projects
conduct
master's
theses
topics
related
model
organisms
in
our
department.
Issues
surrounding
animals
education
are
currently
subject
much
discussion.
Considerable
attention
being
paid
future
animal-free
alternatives.
The
described
here
addresses
issue.
