Cell stem cell,
Journal Year:
2024,
Volume and Issue:
31(3), P. 359 - 377.e10
Published: March 1, 2024
Mitochondrial
fatty
acid
oxidation
(FAO)
is
essential
for
hematopoietic
stem
cell
(HSC)
self-renewal;
however,
the
mechanism
by
which
mitochondrial
metabolism
controls
HSC
fate
remains
unknown.
Here,
we
show
that
within
lineage,
HSCs
have
largest
NADPH
pools,
are
required
proper
and
homeostasis.
Bioinformatic
analysis
of
transcriptome,
biochemical
assays,
genetic
inactivation
FAO
all
indicate
FAO-generated
fuels
cholesterol
synthesis
in
HSCs.
Interference
with
disturbs
segregation
toward
corresponding
daughter
cells
upon
single
division.
Importantly,
found
FAO-NADPH-cholesterol
axis
drives
extracellular
vesicle
(EV)
biogenesis
release
HSCs,
while
inhibition
EV
signaling
impairs
self-renewal.
These
data
reveal
existence
a
NADPH-cholesterol
homeostasis
highlight
non-stochastic
nature
determination.
Cell,
Journal Year:
2024,
Volume and Issue:
187(12), P. 3120 - 3140.e29
Published: May 6, 2024
Non-hematopoietic
cells
are
essential
contributors
to
hematopoiesis.
However,
heterogeneity
and
spatial
organization
of
these
in
human
bone
marrow
remain
largely
uncharacterized.
We
used
single-cell
RNA
sequencing
(scRNA-seq)
profile
29,325
non-hematopoietic
discovered
nine
transcriptionally
distinct
subtypes.
simultaneously
profiled
53,417
hematopoietic
predicted
their
interactions
with
subsets.
employed
co-detection
by
indexing
(CODEX)
spatially
over
1.2
million
cells.
integrated
scRNA-seq
CODEX
data
link
cellular
signaling
proximity.
Our
analysis
revealed
a
hyperoxygenated
arterio-endosteal
neighborhood
for
early
myelopoiesis,
an
adipocytic
localization
stem
progenitor
(HSPCs).
our
atlas
annotate
new
images
uncovered
mesenchymal
stromal
cell
(MSC)
expansion
neighborhoods
co-enriched
leukemic
blasts
MSCs
acute
myeloid
leukemia
(AML)
patient
samples.
This
resolved,
multiomic
provides
reference
investigation
that
drive
Nature Methods,
Journal Year:
2024,
Volume and Issue:
21(5), P. 868 - 881
Published: Feb. 19, 2024
The
human
bone
marrow
(BM)
niche
sustains
hematopoiesis
throughout
life.
We
present
a
method
for
generating
complex
BM-like
organoids
(BMOs)
from
induced
pluripotent
stem
cells
(iPSCs).
BMOs
consist
of
key
cell
types
that
self-organize
into
spatially
defined
three-dimensional
structures
mimicking
cellular,
structural
and
molecular
characteristics
the
hematopoietic
microenvironment.
Functional
properties
include
presence
an
in
vivo-like
vascular
network,
multipotent
mesenchymal
stem/progenitor
cells,
support
neutrophil
differentiation
responsiveness
to
inflammatory
stimuli.
Single-cell
RNA
sequencing
revealed
heterocellular
composition
including
(HSPC)
cluster
expressing
genes
fetal
HSCs.
BMO-derived
HSPCs
also
exhibited
lymphoid
potential
subset
demonstrated
transient
engraftment
upon
xenotransplantation
mice.
show
could
enable
modeling
developmental
aspects
inborn
errors
hematopoiesis,
as
shown
VPS45
deficiency.
Thus,
iPSC-derived
serve
physiologically
relevant
vitro
model
BM
microenvironment
study
development
diseases.
Cell stem cell,
Journal Year:
2024,
Volume and Issue:
31(3), P. 359 - 377.e10
Published: March 1, 2024
Mitochondrial
fatty
acid
oxidation
(FAO)
is
essential
for
hematopoietic
stem
cell
(HSC)
self-renewal;
however,
the
mechanism
by
which
mitochondrial
metabolism
controls
HSC
fate
remains
unknown.
Here,
we
show
that
within
lineage,
HSCs
have
largest
NADPH
pools,
are
required
proper
and
homeostasis.
Bioinformatic
analysis
of
transcriptome,
biochemical
assays,
genetic
inactivation
FAO
all
indicate
FAO-generated
fuels
cholesterol
synthesis
in
HSCs.
Interference
with
disturbs
segregation
toward
corresponding
daughter
cells
upon
single
division.
Importantly,
found
FAO-NADPH-cholesterol
axis
drives
extracellular
vesicle
(EV)
biogenesis
release
HSCs,
while
inhibition
EV
signaling
impairs
self-renewal.
These
data
reveal
existence
a
NADPH-cholesterol
homeostasis
highlight
non-stochastic
nature
determination.
