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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...

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Detalles Bibliográficos
Autores principales: Yue, Feng, Oprescu, Stephanie N., Qiu, Jiamin, Gu, Lijie, Zhang, Lijia, Chen, Jingjuan, Narayanan, Naagarajan, Deng, Meng, Kuang, Shihuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
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
Descripción
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.