ABSTRACT
Dorsal
interneurons
(dIs)
in
the
spinal
cord
encode
perception
of
touch,
pain,
heat,
itchiness
and
proprioception.
Previous
studies
using
genetic
strategies
animal
models
have
revealed
important
insights
into
dI
development,
but
molecular
details
how
dIs
arise
as
distinct
populations
neurons
remain
incomplete.
We
developed
a
resource
to
investigate
fate
specification
by
combining
single-cell
RNA-Seq
atlas
mouse
embryonic
stem
cell-derived
with
pseudotime
analyses.
To
validate
this
silico
useful
tool,
we
used
it
first
identify
genes
that
are
candidates
for
directing
transition
states
lead
lineage
trajectories,
then
validated
them
situ
hybridization
analyses
developing
vivo.
also
identified
an
endpoint
dI5
trajectory
found
become
more
transcriptionally
homogeneous
during
terminal
differentiation.
This
study
introduces
valuable
tool
further
discovery
about
timing
gene
expression
differentiation
demonstrates
its
utility
clarifying
relationships.
ABSTRACT
Stem-cell-based
embryo
models
have
allowed
greater
insight
into
peri-implantation
mammalian
developmental
events
that
are
otherwise
difficult
to
manipulate
due
the
inaccessibility
of
early
embryo.
The
rapid
development
this
field
has
resulted
in
precise
roles
frequently
used
supplements
such
as
N2,
B27
and
Chiron
driving
stem
cell
lineage
commitment
not
being
clearly
defined.
Here,
we
investigate
effects
these
on
embryoid
bodies
better
understand
their
differentiation.
We
show
Wnt
signalling
a
general
posteriorising
effect
aggregates
directs
differentiation
towards
mesoderm,
confirmed
through
upregulation
posterior
mesodermal
markers.
N2
can
mitigate
upregulate
expression
anterior
To
control
gradient
subsequent
versus
fate,
make
use
BMP4
centre
conditions
express
cephalic
These
findings
indicate
there
is
an
intricate
balance
between
various
culture
ability
guide
models.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Окт. 14, 2022
Abstract
Differential
speeds
in
biochemical
reactions
have
been
proposed
to
be
responsible
for
the
differences
developmental
tempo
between
mice
and
humans.
However,
underlying
mechanism
controlling
species-specific
kinetics
remains
determined.
Using
vitro
differentiation
of
pluripotent
stem
cells,
we
recapitulated
segmentation
clocks
diverse
mammalian
species
varying
body
weight
taxa:
marmoset,
rabbit,
cattle
rhinoceros.
Together
with
mouse
human,
clock
periods
six
did
not
scale
animal
weight,
but
were
rather
grouped
according
phylogeny.
The
core
gene
HES7
displayed
clear
scaling
period.
cellular
metabolic
rates
show
an
evident
correlation.
Instead,
genes
involving
showed
expression
pattern
that
scales
Altogether,
our
cell
zoo
uncovered
general
laws
governing
tempo.*
ABSTRACT
Dorsal
interneurons
(dIs)
in
the
spinal
cord
encode
perception
of
touch,
pain,
heat,
itchiness
and
proprioception.
Previous
studies
using
genetic
strategies
animal
models
have
revealed
important
insights
into
dI
development,
but
molecular
details
how
dIs
arise
as
distinct
populations
neurons
remain
incomplete.
We
developed
a
resource
to
investigate
fate
specification
by
combining
single-cell
RNA-Seq
atlas
mouse
embryonic
stem
cell-derived
with
pseudotime
analyses.
To
validate
this
silico
useful
tool,
we
used
it
first
identify
genes
that
are
candidates
for
directing
transition
states
lead
lineage
trajectories,
then
validated
them
situ
hybridization
analyses
developing
vivo.
also
identified
an
endpoint
dI5
trajectory
found
become
more
transcriptionally
homogeneous
during
terminal
differentiation.
This
study
introduces
valuable
tool
further
discovery
about
timing
gene
expression
differentiation
demonstrates
its
utility
clarifying
relationships.