Lipid droplet dynamics regulate adult muscle stem cell fate

Feng Yue; Stephanie N Oprescu; Jiamin Qiu; Lijie Gu; Lijia Zhang; Jingjuan Chen; Naagarajan Narayanan; Meng Deng; Shihuan Kuang

doi:10.1016/j.celrep.2021.110267

Lipid droplet dynamics regulate adult muscle stem cell fate

Cell Rep. 2022 Jan 18;38(3):110267. doi: 10.1016/j.celrep.2021.110267.

Authors

Feng Yue¹, Stephanie N Oprescu², Jiamin Qiu³, Lijie Gu³, Lijia Zhang³, Jingjuan Chen³, Naagarajan Narayanan⁴, Meng Deng⁴, Shihuan Kuang⁵

Affiliations

¹ Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: fyue@purdue.edu.
² Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
³ Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
⁴ Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA.
⁵ Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: skuang@purdue.edu.

Abstract

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.

Keywords: ATGL; asymmetric division; metabolism; muscle satellite cell; oxidative stress; regeneration; self-renewal.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Lipid Droplets / metabolism*
Mice
Muscle Development / physiology*
Muscle, Skeletal / physiology*
Regeneration / physiology
Satellite Cells, Skeletal Muscle / metabolism*

Abstract

Publication types

MeSH terms

Grants and funding