Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.

Abstract:

:During growth, homeostasis and regeneration, stem cells are exposed to different energy demands. Here, we characterise the metabolic pathways that mediate the commitment and differentiation of mouse skeletal muscle stem cells, and how their modulation can influence the cell state. We show that quiescent satellite stem cells have low energetic demands and perturbed oxidative phosphorylation during ageing, which is also the case for cells from post-mortem tissues. We show also that myogenic fetal cells have distinct metabolic requirements compared to those proliferating during regeneration, with the former displaying a low respiration demand relying mostly on glycolysis. Furthermore, we show distinct requirements for peroxisomal and mitochondrial fatty acid oxidation (FAO) in myogenic cells. Compromising peroxisomal but not mitochondrial FAO promotes early differentiation of myogenic cells. Acute muscle injury and pharmacological block of peroxisomal and mitochondrial FAO expose differential requirements for these organelles during muscle regeneration. Taken together, these observations indicate that changes in myogenic cell state lead to significant alterations in metabolic requirements. In addition, perturbing specific metabolic pathways impacts on myogenic cell fates and the regeneration process.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Pala F,Di Girolamo D,Mella S,Yennek S,Chatre L,Ricchetti M,Tajbakhsh S

doi

10.1242/jcs.212977

subject

Has Abstract

pub_date

2018-07-27 00:00:00

issue

14

eissn

0021-9533

issn

1477-9137

pii

131/14/jcs212977

journal_volume

131

pub_type

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