期刊
CELL REPORTS
卷 38, 期 3, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.110267
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资金
- Muscular Dystrophy Association [MDA516161]
- Purdue Center for Cancer Research [NIH-P30CA023168]
- NIH Shared Instrumentation Grant [S10DO20029]
- [NIH-R01AR071649]
- [NIH-R03AR068108]
- [NIH-F31AR077424]
In skeletal muscle satellite cells, the dynamic distribution of lipid droplets determines cell fate, with LDLow cells outperforming LDHigh cells in regeneration and self-renewal. Interventions in LD biogenesis and catabolism disrupt cell fate balance and impair the regenerative capacity of SCs.
The lipid droplet (LD) is a central hub for fatty acid metabolism in cells. Here we define the dynamics and explore the role of LDs in skeletal muscle satellite cells (SCs), a stem cell population responsible for muscle regeneration. In newly divided SCs, LDs are unequally distributed in sister cells exhibiting asymmetric cell fates, as the LDLow cell self-renews while the LDHigh cell commits to differentiation. When transplanted into regenerating muscles, LDLow cells outperform LDHigh cells in self-renewal and regeneration in vivo. Pharmacological inhibition of LD biogenesis or genetic inhibition of LD catabolism through knockout of Pnpla2 (encoding ATGL, the rate-limiting enzyme for lipolysis) disrupts cell fate homeostasis and impairs the regenerative capacity of SCs. Dysfunction of Pnpla2-null SCs is associated with energy insufficiency and oxidative stress that can be partially rescued by antioxidant (N-acetylcysteine) treatment. These results establish a direct link between LD dynamics and stem cell fate determination.
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