First Author | Yue F | Year | 2022 |
Journal | Cell Rep | Volume | 38 |
Issue | 3 | Pages | 110267 |
PubMed ID | 35045287 | Mgi Jnum | J:327098 |
Mgi Id | MGI:6879564 | Doi | 10.1016/j.celrep.2021.110267 |
Citation | Yue F, et al. (2022) Lipid droplet dynamics regulate adult muscle stem cell fate. Cell Rep 38(3):110267 |
abstractText | 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 LD(Low) cell self-renews while the LD(High) cell commits to differentiation. When transplanted into regenerating muscles, LD(Low) cells outperform LD(High) 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. |