About
70%
of
human
cleavage
stage
embryos
show
chromosomal
mosaicism,
falling
to
20%
in
blastocysts.
Chromosomally
mosaic
blastocysts
can
implant
and
lead
healthy
new-borns
with
normal
karyotypes.
Studies
mouse
gastruloids
showed
that
aneuploid
cells
are
eliminated
from
the
epiblast
by
p53-mediated
apoptosis
while
being
tolerated
trophectoderm.
These
observations
suggest
a
selective
loss
embryos,
but
underlying
mechanisms
not
yet
fully
understood.
Here,
we
investigated
cellular
consequences
aneuploidy
total
125
RNA-sequencing
trophectoderm
activated
p53
pathway
proportionate
level
imbalance.
Immunostaining
corroborated
triggers
proteotoxic
stress,
autophagy,
p53-signaling,
independent
DNA
damage.
Total
cell
numbers
were
lower
due
decline
both
epiblast/primitive
endoderm
numbers.
While
may
be
attributed
apoptosis,
impaired
second
lineage
segregation,
particularly
primitive
formation.
This
might
reinforced
retention
NANOG.
Our
findings
explain
why
fail
further
develop
hypothesize
same
removal
embryos.
Cell,
Год журнала:
2024,
Номер
187(11), С. 2838 - 2854.e17
Опубликована: Май 1, 2024
Retrospective
lineage
reconstruction
of
humans
predicts
that
dramatic
clonal
imbalances
in
the
body
can
be
traced
to
2-cell
stage
embryo.
However,
whether
and
how
such
asymmetries
arise
embryo
is
unclear.
Here,
we
performed
prospective
tracing
human
embryos
using
live
imaging,
non-invasive
cell
labeling,
computational
predictions
determine
contribution
each
blastomere
epiblast
(body),
hypoblast
(yolk
sac),
trophectoderm
(placenta).
We
show
majority
cells
originate
from
only
one
observe
three
become
internalized
at
8-to-16-cell
transition.
Moreover,
these
are
more
frequently
derived
first
divide
stage.
propose
division
dynamics
a
internalization
bottleneck
early
establish
asymmetry
composition
future
body.
Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(6)
Опубликована: Янв. 4, 2024
Aneuploidy,
a
deviation
from
the
normal
chromosome
copy
number,
is
common
in
human
embryos
and
considered
primary
cause
of
implantation
failure
early
pregnancy
loss.
Meiotic
errors
lead
to
uniformly
abnormal
karyotypes,
while
mitotic
chromosomal
mosaicism:
presence
cells
with
at
least
two
different
karyotypes
within
an
embryo.
Knowledge
about
mosaicism
blastocysts
mainly
derives
bulk
DNA
sequencing
multicellular
trophectoderm
(TE)
and/or
inner
cell
mass
(ICM)
samples.
However,
this
can
only
detect
average
net
gain
or
loss
above
detection
threshold
20-30%.
To
accurately
assess
mosaicism,
we
separated
TE
ICM
55
good
quality
surplus
successfully
applied
single-cell
whole
genome
(scKaryo-seq)
on
1057
cells.
Mosaicism
involving
numerical
structural
abnormalities
was
detected
82%
embryos,
where
most
affected
less
than
20%
Structural
abnormalities,
potentially
caused
by
replication
stress
damage,
were
observed
69%
embryos.
In
conclusion,
our
findings
indicated
that
prevalent
good-quality
blastocysts,
these
would
likely
be
identified
as
current
techniques
used
for
preimplantation
genetic
testing
aneuploidy
(PGT-A).
Developmental Biology,
Год журнала:
2024,
Номер
509, С. 43 - 50
Опубликована: Фев. 5, 2024
Understanding
the
processes
and
mechanisms
underlying
early
human
embryo
development
has
become
an
increasingly
active
important
area
of
research.
It
potential
for
insights
into
clinical
issues
such
as
pregnancy
loss,
origins
congenital
anomalies
developmental
adult
disease,
well
fundamental
biology.
Improved
culture
systems
preimplantation
embryos,
combined
with
new
tools
single
cell
genomics
live
imaging,
are
providing
similarities
differences
between
mouse
development.
However,
access
to
material
is
still
restricted
extended
embryos
regulatory
ethical
concerns.
Stem
cell-derived
models
different
phases
can
potentially
overcome
these
limitations
provide
a
scalable
source
explore
postimplantation
stages
To
date,
clearly
incomplete
replicas
normal
but
future
technological
improvements
be
envisaged.
The
environment
studies
remains
fully
resolved.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июнь 25, 2024
Abstract
During
human
embryonic
development,
early
cleavage-stage
embryos
are
more
susceptible
to
errors.
Studies
have
shown
that
many
problems
occur
during
the
first
mitosis,
such
as
direct
cleavage,
chromosome
segregation
errors,
and
multinucleation.
However,
mechanisms
whereby
these
errors
mitosis
in
remain
unknown.
To
clarify
this
aspect,
present
study,
we
image
discarded
living
two-pronuclear
stage
zygotes
using
fluorescent
labeling
confocal
microscopy
without
microinjection
of
DNA
or
mRNA
investigate
association
between
spindle
shape
nuclear
abnormality
mitosis.
We
observe
mitotic
spindles
vary,
low-aspect-ratio-shaped
tend
lead
formation
multiple
nuclei
at
2-cell
stage.
Moreover,
defocusing
poles
spindles,
which
strongly
associated
with
Additionally,
show
differences
positions
centrosomes
cause
Furthermore,
multinuclei
modified
form
mononuclei
after
second
because
occurrence
pole
is
firmly
reduced.
Our
study
will
contribute
markedly
research
on
cleavage
embryos.
Stem Cell Reports,
Год журнала:
2025,
Номер
unknown, С. 102506 - 102506
Опубликована: Май 1, 2025
Human
pluripotent
stem
cells
(hPSCs)
maintain
diploid
populations
for
generations
despite
frequent
mitotic
errors
that
cause
aneuploidy
or
chromosome
imbalances.
Consequently,
aneuploid
hPSC
propagation
must
be
prevented
to
sustain
genome
stability,
but
how
this
is
achieved
unknown.
Surprisingly,
we
find
that,
unlike
somatic
cells,
uniformly
with
heterogeneous
abnormal
karyotypes
proliferate.
Instead,
in
mosaic
populations,
cell-non-autonomous
competition
between
neighboring
and
hPSCs
eliminates
less
fit
regardless
of
specific
Aneuploid
lower
MYC
higher
p53
levels
relative
neighbors
are
outcompeted
conversely
gain
an
advantage
when
abundance
switches.
Thus,
MYC-
p53-driven
cell
preserves
integrity
their
low
fidelity
intrinsic
capacity
proliferate
genome.
These
findings
have
important
implications
using
regenerative
medicine
human
embryos
form
during
development
the
prevalence
aneuploidy.
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Фев. 5, 2024
Mammalian
preimplantation
embryos
often
contend
with
aneuploidy
that
arose
either
by
the
inheritance
of
meiotic
errors
from
gametes,
or
mitotic
mis-segregation
events
occurred
following
fertilization.
Regardless
origin,
mis-segregated
chromosomes
become
encapsulated
in
micronuclei
(MN)
are
spatially
isolated
main
nucleus.
Much
our
knowledge
MN
formation
comes
dividing
somatic
cells
during
tumorigenesis,
but
error-prone
cleavage-stage
early
embryogenesis
is
fundamentally
different.
One
unique
aspect
cellular
fragmentation
(CF),
whereby
small
subcellular
bodies
pinch
off
embryonic
blastomeres,
frequently
observed.
CF
has
been
detected
both
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 8, 2024
Abstract
In
developmental
biology
and
in
vitro
fertilization
(IVF),
image-based
assessment
of
embryos
is
pivotal.
Traditional
methods
clinical
IVF
have
been
constrained
to
2D
morpho-kinetic
profiling
manual
selection,
hindered
by
the
absence
noninvasive
techniques
for
quantitative
3D
imaging
over
extended
durations.
Here,
we
overcome
these
limitations
employing
low-coherence
holotomography
monitor
mouse
preimplantation
embryo
development
from
2-cell
stage
expanded
blastocyst.
This
approach
enables
generation
refractive
index
tomograms
unlabeled
embryos,
facilitating
observation
subcellular
dynamics.
We
investigated
spatiotemporal
profiles
development,
identifying
key
parameters
that
distinguish
between
with
differing
outcomes—specifically,
Grade
A
successfully
progressed
blastocysts
within
72
hours,
C
did
not.
Using
machine
learning,
demonstrate
can
offer
a
noninvasive,
framework
predicting
high
potential.
