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Lipid droplet dynamics regulate adult muscle stem cell fate
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 cell...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127130/ https://www.ncbi.nlm.nih.gov/pubmed/35045287 http://dx.doi.org/10.1016/j.celrep.2021.110267 |
Sumario: | 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. |
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