GEO series
A NAD + Metabolic Checkpoint Regulates Hematopoietic Stem Cell Activation and Aging
GSE268310
Mus musculus
Expression profiling by high throughput sequencing
12 samples
2024/05/28
GPL21103
Summary
How hematopoietic stem cells (HSCs) maintain metabolic homeostasis to support tissue repair and regeneration throughout the lifespan is elusive. Here we show that CD38, a NAD+ metabolic enzyme, promotes HSC proliferation by inducing mitochondrial Ca2+ influx and mitochondrial metabolism at young age. Conversely, aberrant CD38 upregulation during aging is a driver of HSC deterioration due to compromised mitochondrial stress management. Pharmacological inactivation of CD38 reverses HSC aging and the pathophysiological changes of the aging hematopoietic system. Blocking mitochondrial Ca2+ influx inhibits HSC proliferation at young age yet prevents HSC aging. Our study highlights a NAD+ metabolic checkpoint that balances mitochondrial activation to support HSC proliferation and mitochondrial stress to enhance HSC self-renewal throughout the lifespan, and links aberrant Ca2+ signaling to HSC aging.
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Paper (PMID 39044033) ↗
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