PGC-1α in the myofibers regulates the balance between myogenic and adipogenic progenitors affecting muscle regeneration

Marc Beltrà; Fabrizio Pin; Domiziana Costamagna; Robin Duelen; Alessandra Renzini; Riccardo Ballarò; Lorena Garcia-Castillo; Ambra Iannuzzi; Viviana Moresi; Dario Coletti; Maurilio Sampaolesi; Fabio Penna; Paola Costelli

doi:10.1016/j.isci.2022.105480

PGC-1α in the myofibers regulates the balance between myogenic and adipogenic progenitors affecting muscle regeneration

iScience. 2022 Nov 2;25(11):105480. doi: 10.1016/j.isci.2022.105480. eCollection 2022 Nov 18.

Authors

Marc Beltrà^{1

2}, Fabrizio Pin¹, Domiziana Costamagna³, Robin Duelen³, Alessandra Renzini⁴, Riccardo Ballarò¹, Lorena Garcia-Castillo^{1

2}, Ambra Iannuzzi¹, Viviana Moresi⁴, Dario Coletti⁴, Maurilio Sampaolesi^{3

4}, Fabio Penna^{1

2}, Paola Costelli^{1

2}

Affiliations

¹ Experimental Medicine and Clinical Pathology Unit, Department of Clinical and Biological Sciences, University of Torino, Corso Raffaello 30, 10125 Turin, Italy.
² Interuniversity Institute of Myology (IIM), 61029 Urbino, Italy.
³ Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium.
⁴ Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Sapienza University of Rome, 00161 Rome, Italy.

Abstract

Skeletal muscle repair is accomplished by satellite cells (MuSCs) in cooperation with interstitial stromal cells (ISCs), but the relationship between the function of these cells and the metabolic state of myofibers remains unclear. This study reports an altered proportion of MuSCs and ISCs (including adipogenesis-regulatory cells; Aregs) induced by the transgenic overexpression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the myofibers (MCK-PGC-1α mice). Although PGC-1α-driven increase of MuSCs does not accelerate muscle regeneration, myogenic progenitors isolated from MCK-PGC-1α mice and transplanted into intact and regenerating muscles are more prone to fuse with recipient myofibers than those derived from wild-type donors. Moreover, both young and aged MCK-PGC-1α animals exhibit reduced perilipin-positive areas when challenged with an adipogenic stimulus, demonstrating low propensity to accumulate adipocytes within the muscle. Overall, these results unveil that increased PGC-1α expression in the myofibers favors pro-myogenic and anti-adipogenic cell populations in the skeletal muscle.

Keywords: Cell biology; Developmental biology; Physiology.