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.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Июнь 15, 2022
Abstract
Following
gastrulation,
the
three
primary
germ
layers
develop
into
major
organs
in
a
process
known
as
organogenesis.
Single-cell
RNA
sequencing
has
enabled
profiling
of
gene
expression
dynamics
these
cell
fate
decisions,
yet
comprehensive
map
interplay
between
transcription
factors
and
cis-regulatory
elements
is
lacking,
are
underlying
regulatory
networks.
Here
we
generate
multi-omics
atlas
mouse
early
organogenesis
by
simultaneously
chromatin
accessibility
from
tens
thousands
single
cells.
We
computational
method
to
leverage
multimodal
readouts
predict
factor
binding
events
elements,
which
then
use
infer
networks
that
underpin
lineage
commitment
events.
Finally,
show
models
can
be
used
silico
predictions
effect
perturbations.
validate
this
experimentally
showing
Brachyury
essential
for
differentiation
neuromesodermal
progenitors
somitic
mesoderm
priming
elements.
The
data
set
interactively
explored
at
https://www.bioinformatics.babraham.ac.uk/shiny/shiny_multiome_organogenesis/
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.
Limited
color
channels
in
fluorescence
microscopy
have
long
constrained
spatial
analysis
biological
specimens.
Here,
we
introduce
cycle
Hybridization
Chain
Reaction
(HCR),
a
method
that
integrates
multicycle
DNA
barcoding
with
HCR
to
overcome
this
limitation.
cycleHCR
enables
highly
multiplexed
imaging
of
RNA
and
proteins
using
unified
barcode
system.
Whole-embryo
transcriptomics
achieved
precise
three-dimensional
gene
expression
cell
fate
mapping
across
specimen
depth
~310
μm.
When
combined
expansion
microscopy,
revealed
an
intricate
network
10
subcellular
structures
mouse
embryonic
fibroblasts.
In
hippocampal
slices,
multiplex
protein
uncovered
complex
gradients
cell-type-specific
nuclear
structural
variations.
provides
quantitative
framework
for
elucidating
regulation
deep
tissue
contexts
research
potentially
diagnostic
applications.
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.
