bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 11, 2024
Summary
Understanding
the
diversification
of
mammalian
cell
lineages
is
an
essential
to
embryonic
development,
organ
regeneration
and
tissue
engineering.
Shortly
after
implantation
in
uterus,
pluripotent
cells
epiblast
generate
three
germ
layers:
ectoderm,
mesoderm
endoderm
1
.
Although
clonal
analyses
suggest
early
specification
towards
particular
2–4
,
single-cell
transcriptomes
do
not
identify
lineage-specific
markers
5–11
thus,
molecular
regulation
such
remains
unknow.
Here,
we
studied
epigenetic
landscape
single
cells,
which
revealed
lineage
priming
endoderm,
ectoderm
or
mesoderm.
Unexpectedly,
with
mesodermal
show
a
strong
signature
for
endothelial/endocardial
fate,
suggesting
this
aside
from
other
Through
analysis
live
imaging,
that
endothelial
precursors
divergence
rest
derivatives.
In
particular,
cardiomyocytes
endocardial
limited
relationship,
despite
being
temporally
spatially
co-recruited
during
gastrulation.
Furthermore,
analysing
tracks
through
unsupervised
classification
migratory
activity,
found
behavioral
shortly
onset
migration
cardiogenic
area.
These
results
provide
new
model
phenotypically
silent
modify
current
knowledge
on
sequence
timing
cardiovascular
2,13
The
placenta
is
one
of
the
most
important
yet
least
understood
organs.
Due
to
limitations
conventional
research
approaches,
we
are
still
far
from
a
comprehensive
understanding
mouse
placentation,
especially
regarding
differentiation
trophoblast
lineages
at
early
developmental
stage.
To
decipher
cell
compositions
and
processes,
systematically
profile
single-cell
transcriptomes
cells
extraembryonic
tissues
(embryonic
day
7.5
(E7.5)
E8.5)
placentae
(E9.5-E14.5)
one-day
intervals.
We
identify
distinct
types
during
including
unreported
progenitor
intermediate
precursor
cells.
An
updated
roadmap
presented
following
systematic
transcriptome
analyses.
Based
on
transcriptomic
regulatory
network
inference,
specify
transcription
factors
responsible
for
regulation
dynamic
processes
lineage
diversification.
map
trajectories
find
that
sinusoid
giant
arise
subpopulation
ectoplacental
cone
provide
data
resource
shed
light
future
mechanistic
studies
gene
networks
governing
hemochorial
placentation.
Nature,
Год журнала:
2023,
Номер
626(7998), С. 367 - 376
Опубликована: Дек. 13, 2023
Abstract
Implantation
of
the
human
embryo
begins
a
critical
developmental
stage
that
comprises
profound
events
including
axis
formation,
gastrulation
and
emergence
haematopoietic
system
1,2
.
Our
mechanistic
knowledge
this
window
life
remains
limited
due
to
restricted
access
in
vivo
samples
for
both
technical
ethical
reasons
3–5
Stem
cell
models
have
emerged
help
unlock
mysteries
6–16
Here
we
present
genetically
inducible
stem
cell-derived
embryoid
model
early
post-implantation
embryogenesis
captures
reciprocal
codevelopment
embryonic
tissue
extra-embryonic
endoderm
mesoderm
niche
with
haematopoiesis.
This
is
produced
from
induced
pluripotent
cells
shows
unanticipated
self-organizing
cellular
programmes
similar
those
occur
embryogenesis,
formation
amniotic
cavity
bilaminar
disc
morphologies
as
well
generation
an
anterior
hypoblast
pole
posterior
domain.
The
layer
these
embryoids
lacks
trophoblast
advanced
multilineage
yolk
sac
tissue-like
morphogenesis
harbours
process
distinct
waves
haematopoiesis,
erythroid-,
megakaryocyte-,
myeloid-
lymphoid-like
cells.
presents
easy-to-use,
high-throughput,
reproducible
scalable
platform
probe
multifaceted
aspects
development
blood
at
stage.
It
will
provide
tractable
human-based
drug
testing
disease
modelling.
Developmental Cell,
Год журнала:
2024,
Номер
59(12), С. 1489 - 1505.e14
Опубликована: Апрель 4, 2024
Embryogenesis
requires
substantial
coordination
to
translate
genetic
programs
the
collective
behavior
of
differentiating
cells,
but
understanding
how
cellular
decisions
control
tissue
morphology
remains
conceptually
and
technically
challenging.
Here,
we
combine
continuous
Cas9-based
molecular
recording
with
a
mouse
embryonic
stem
cell-based
model
trunk
build
single-cell
phylogenies
that
describe
transient,
multipotent
neuro-mesodermal
progenitors
(NMPs)
as
they
commit
into
neural
somitic
cell
types.
We
find
NMPs
show
subtle
transcriptional
signatures
related
their
recent
differentiation
contribute
downstream
lineages
through
surprisingly
broad
distribution
individual
fate
outcomes.
Although
decision-making
can
be
heavily
influenced
by
environmental
cues
induce
morphological
phenotypes,
axial
intrinsically
mature
over
developmental
time
favor
lineage.
Using
these
data,
present
an
experimental
analytical
framework
for
exploring
non-homeostatic
dynamics
transient
progenitor
populations
shape
complex
tissues
during
critical
windows.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 20, 2024
Recent
technological
advancements
in
single-cell
genomics
have
enabled
joint
profiling
of
gene
expression
and
alternative
modalities
at
unprecedented
scale.
Consequently,
the
complexity
multi-omics
data
sets
is
increasing
massively.
Existing
models
for
multi-modal
are
typically
limited
functionality
or
scalability,
making
integration
downstream
analysis
cumbersome.
We
present
multiDGD,
a
scalable
deep
generative
model
providing
probabilistic
framework
to
learn
shared
representations
transcriptome
chromatin
accessibility.
It
shows
outstanding
performance
on
reconstruction
without
feature
selection.
demonstrate
several
from
human
mouse
that
multiDGD
learns
well-clustered
representations.
further
find
modeling
sample
covariates
enables
post-hoc
need
fine-tuning.
Additionally,
we
show
can
detect
statistical
associations
between
genes
regulatory
regions
conditioned
learned
available
as
an
scverse-compatible
package
GitHub.
Understanding
requires
powerful
solutions.
Here,
authors
data-efficient
machine
learning
approach
paired
data.
unseen
link
distal
elements
promoters,
presenting
computational
version
HiC.
Epigenetic
modifications
of
chromatin
are
essential
for
the
establishment
cell
identities
during
embryogenesis.
Between
embryonic
days
3.5–7.5
murine
development,
major
lineage
decisions
made
that
discriminate
extraembryonic
and
tissues,
primary
germ
layers
formed,
thereby
laying
down
basic
body
plan.
In
this
review,
we
cover
contribution
dynamic
by
DNA
methylation,
changes
accessibility,
histone
modifications,
in
combination
with
transcription
factors
control
gene
expression
programs
different
types.
We
highlight
differences
regulation
enhancer
promoter
marks
discuss
their
requirement
specification.
Importantly,
many
cases,
lineage‐specific
targeting
epigenetic
modifiers
is
carried
out
pioneer
or
master
factors,
sum
mediate
landscape
cell‐type‐specific
thus,
identities.
Journal of Medical Ethics,
Год журнала:
2021,
Номер
47(12), С. e66 - e66
Опубликована: Фев. 2, 2021
For
the
past
40
years,
14-day
rule
has
governed
and,
by
defining
a
clear
boundary,
enabled
embryo
research
and
clinical
benefits
derived
from
this.
It
been
both
piece
of
legislation
good
practice
globally.
However,
methods
now
allow
embryos
to
be
cultured
for
more
than
14
days,
something
difficult
imagine
when
was
established,
knowledge
gained
in
intervening
years
provides
robust
scientific
rationale
why
it
is
essential
conduct
on
later
stage
human
embryos.
In
this
paper,
I
argue
that
current
limit
vitro
should
extended
28
days
permit
will
illuminate
our
beginnings
as
well
provide
new
therapeutic
possibilities
reduce
miscarriage
developmental
abnormalities.
also
validation
potentially
useful
alternatives.
Through
consideration
ethical
arguments,
conclude
there
are
no
coherent
or
persuasive
reasons
deny
researchers,
through
them
humanity,
innovation
generate.
