Development,
Journal Year:
2024,
Volume and Issue:
151(2)
Published: Jan. 15, 2024
Berna
Sozen
is
an
Assistant
Professor
in
the
Department
of
Genetics
at
Yale
University,
USA.
Berna's
lab
studies
early
mammalian
development,
metabolism,
and
maternal–fetal
interactions
using
mouse
human
embryos,
as
well
stem
cell-derived
embryo-like
models.
In
2022,
received
NIH
Director's
New
Innovator
Award.
We
spoke
to
over
Zoom
learn
more
about
her
journey
becoming
a
group
leader
importance
making
science
careers
accessible.
Developmental Cell,
Journal Year:
2024,
Volume and Issue:
59(12), P. 1523 - 1537.e6
Published: April 17, 2024
Patterning
and
growth
are
fundamental
features
of
embryonic
development
that
must
be
tightly
coordinated.
To
understand
how
metabolism
impacts
early
mesoderm
development,
we
used
mouse
stem-cell-derived
gastruloids,
co-expressed
glucose
transporters
with
the
mesodermal
marker
T/Bra.
We
found
mimic,
2-deoxy-D-glucose
(2-DG),
blocked
T/Bra
expression
abolished
axial
elongation
in
gastruloids.
However,
removal
did
not
phenocopy
2-DG
treatment
despite
a
decline
glycolytic
intermediates.
As
can
also
act
as
competitive
inhibitor
mannose
protein
glycosylation,
added
together
it
could
rescue
specification
both
vivo
vitro.
further
showed
blocking
production
intracellular
recycling
abrogated
specification.
Proteomics
analysis
demonstrated
reversed
glycosylation
Wnt
pathway
regulator,
secreted
frizzled
receptor
Frzb.
Our
study
controls
Nature,
Journal Year:
2024,
Volume and Issue:
634(8035), P. 919 - 928
Published: Oct. 16, 2024
The
prevailing
dogma
for
morphological
patterning
in
developing
organisms
argues
that
the
combined
inputs
of
transcription
factor
networks
and
signalling
morphogens
alone
generate
spatially
temporally
distinct
expression
patterns.
However,
metabolism
has
also
emerged
as
a
critical
developmental
regulator
Journal of Cell Science,
Journal Year:
2024,
Volume and Issue:
137(12)
Published: June 15, 2024
Collective
cell
migration,
where
cells
move
as
a
cohesive
unit,
is
vital
process
underlying
morphogenesis
and
cancer
metastasis.
Thanks
to
recent
advances
in
imaging
modelling,
we
are
beginning
understand
the
intricate
relationship
between
its
microenvironment
how
this
shapes
polarity,
metabolism
modes
of
migration.
The
use
biophysical
mathematical
models
offers
fresh
perspective
on
migrate
collectively,
either
flowing
fluid-like
state
or
transitioning
more
static
states.
Continuing
unite
researchers
biology,
physics
mathematics
will
enable
us
decode
complex
biological
behaviours
that
underly
collective
migration;
only
then
can
coordinated
movement
influences
formation
organisation
tissues
directs
spread
metastatic
cancer.
In
Perspective,
highlight
exciting
discoveries,
emerging
themes
common
challenges
have
arisen
years,
possible
ways
forward
bridge
gaps
our
current
understanding
Development,
Journal Year:
2024,
Volume and Issue:
151(12)
Published: June 15, 2024
The
field
of
developmental
metabolism
is
experiencing
a
technological
revolution
that
opening
entirely
new
fields
inquiry.
Advances
in
metabolomics,
small-molecule
sensors,
single-cell
RNA
sequencing
and
computational
modeling
present
opportunities
for
exploring
cell-specific
tissue-specific
metabolic
networks,
interorgan
communication,
gene-by-metabolite
interactions
time
space.
Together,
these
advances
not
only
means
by
which
biologists
can
tackle
questions
have
challenged
the
centuries,
but
also
young
scientists
with
to
define
areas
These
emerging
frontiers
were
at
center
highly
interactive
2023
EMBO
workshop
'Developmental
metabolism:
flows
energy,
matter,
information'.
Here,
we
summarize
key
discussions
from
this
forum,
emphasizing
modern
biology's
challenges
opportunities.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: June 7, 2023
Abstract
Patterning
and
growth
are
fundamental
features
of
embryonic
development
that
must
be
tightly
coordinated
during
morphogenesis.
As
metabolism
can
control
cell
while
also
providing
mechanistic
links
to
developmental
signalling
pathways,
it
is
ideally
placed
enable
this
coordination.
To
understand
how
impacts
early
mesoderm
specification,
we
used
mouse
stem
(ES)
cell-derived
gastruloids,
as
these
temporal
over
metabolic
manipulations
generated
in
large
quantities.
Gastruloids
show
mosaic
expression
two
glucose
transporters,
Slc2a1
Slc2a3
both
which
co-express
with
the
mesodermal
marker
T/Bra
neural
Sox2
.
significance
cellular
uptake
development,
inhibitor
2-deoxy-D-glucose
(2-DG).
2-DG
specifically
blocks
without
affecting
abolishes
axial
elongation
gastruloids.
Surprisingly,
removing
completely
from
medium
did
not
phenocopy
treatment
despite
a
significant
decline
glycolytic
intermediates
occurring
under
conditions.
act
competitive
mannose,
added
mannose
together
found
could
rescue
specification.
Together,
our
results
crucial
for
pathway
dispensable
at
stages
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 5, 2023
SUMMARY
Mammalian
stem-cell-based
models
of
embryo
development
(stembryos)
hold
great
promise
in
basic
and
applied
research.
However,
considerable
phenotypic
variation
despite
identical
culture
conditions
limits
their
potential.
The
biological
processes
underlying
this
seemingly
stochastic
are
poorly
understood.
Here,
we
investigate
the
roots
by
intersecting
transcriptomic
states
morphological
history
individual
stembryos
across
stages
modeling
post-implantation
early
organogenesis.
Through
machine
learning
integration
time-resolved
single-cell
RNA-sequencing
with
imaging-based
quantitative
profiling,
identify
features
predictive
end-state.
Leveraging
power
revealed
that
imbalance
oxidative
phosphorylation
glycolysis
results
aberrant
morphology
a
neural
lineage
bias
can
be
corrected
metabolic
interventions.
Collectively,
our
work
establishes
divergent
as
drivers
variation,
offers
broadly
applicable
framework
to
chart
predict
organoid
systems.
strategy
leveraged
control
processes,
ultimately
increasing
reproducibility
vitro
Highlights
Time-resolved
charting
hundreds
generates
molecular
fingerprints
Machine
identifies
end-state
Early
cellular
composition
Metabolic
interventions
tune
stembryo
correct
derailment
differentiation
outcomes
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Dec. 18, 2023
Precise
coupling
between
cellular
physiology
and
metabolism
is
emerging
as
a
vital
relationship
underpinning
tissue
health
longevity.
Nevertheless,
functional-metabolic
within
heterogenous
microenvironments
in
vivo
remains
poorly
understood
due
to
complexity
metabolic
plasticity.
Here,
we
establish
the
Drosophila
renal
system
paradigm
for
linking
mechanistic
analysis
of
metabolism,
at
single-cell
resolution,
organ-wide
physiology.
Kidneys
are
amongst
most
energetically-demanding
organs,
yet
exactly
how
individual
cell
types
fine-tune
meet
their
diverse,
unique
physiologies
over
life-course
unclear.
Integrating
live-imaging
metabolite
organelle
dynamics
with
spatio-temporal
genetic
perturbation
intact
functional
tissue,
uncover
distinct
signatures
essential
support
healthy
ageing.
Cell
type-specific
programming
glucose
handling,
PPP-mediated
glutathione
regeneration
FA
β-oxidation
via
dynamic
lipid-peroxisomal
networks,
downstream
differential
ERR
receptor
activity,
precisely
match
energetic
demands
whilst
limiting
damage
premature
senescence;
however,
dramatic
dysregulation
may
underlie
age-related
dysfunction.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 7, 2024
Gastrulation
is
the
highly
coordinated
process
by
which
early
embryo
breaks
symmetry,
establishes
germ
layers
and
a
body
plan,
sets
stage
for
organogenesis.
As
mammalian
development
challenging
to
study
Emerging Topics in Life Sciences,
Journal Year:
2023,
Volume and Issue:
7(4), P. 455 - 464
Published: Dec. 18, 2023
Metabolic
networks
are
well
placed
to
orchestrate
the
coordination
of
multiple
cellular
processes
associated
with
embryonic
development
such
as
cell
growth,
proliferation,
differentiation
and
movement.
Here,
we
discuss
advantages
that
gastruloids,
aggregates
mammalian
stem
cells
self-assemble
a
rudimentary
body
plan,
have
for
uncovering
instructive
role
metabolic
pathways
play
in
directing
developmental
processes.
We
emphasise
importance
using
reductionist
systems
link
specific
defined
events
early
their
utility
obtaining
enough
material
metabolomic
studies.
Finally,
review
ways
which
basic
gastruloid
protocol
can
be
adapted
obtain
models
types,
tissues
regions.
Together,
propose
gastruloids
an
ideal
system
rapidly
uncover
new
mechanistic
links
between
signalling
networks,
then
inform
precise
vivo
studies
confirm
function
embryo.
