The Microenvironment Is a Critical Regulator of Muscle Stem Cell Activation and Proliferation

John H Nguyen,Jin D Chung,James G Ryall,Gordon S Lynch

doi:10.3389/fcell.2019.00254

John H Nguyen, Jin D Chung + Show 2 more

Open Access

https://doi.org/10.3389/fcell.2019.00254

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Abstract

Skeletal muscle has a remarkable capacity to regenerate following injury, a property conferred by a resident population of muscle stem cells (MuSCs). In response to injury, MuSCs must double their cellular content to divide, a process requiring significant new biomass in the form of nucleotides, phospholipids, and amino acids. This new biomass is derived from a series of intracellular metabolic cycles and alternative routing of carbon. In this review, we examine the link between metabolism and skeletal muscle regeneration with particular emphasis on the role of the cellular microenvironment in supporting the production of new biomass and MuSC proliferation.

Highlights

Skeletal muscle has a remarkable potential to regenerate following injury, a property conferred by a population of local somatic stem cells termed muscle stem cells (MuSCs)
The proliferative response of MuSCs to injury is dependent on the capacity of these cells to double their cellular content, requiring synthesis of new biomass in the form of nucleotides, phospholipids, and nonessential amino acids (NEAA) (Koopman et al, 2014; Hosios et al, 2016)
As many skeletal muscle pathologies are linked to a shift in the local metabolic environment (Chi et al, 1987; Joseph et al, 2018), and many metabolic disorders result in impaired skeletal muscle repair (D’Souza et al, 2016; Monaco et al, 2018), it is critical that we understand the link between MuSCs and their local tissue microenvironment

Summary

INTRODUCTION

Skeletal muscle has a remarkable potential to regenerate following injury, a property conferred by a population of local somatic stem cells termed muscle stem cells (MuSCs). MuSCs typically become specified to the myogenic lineage after activation and undergo multiple rounds of proliferation to generate sufficient myonuclei to support protein synthesis and mature muscle formation (Bischoff, 1990) These proliferating myogenic precursors (myoblasts) exit the cell cycle and terminally differentiate to myocytes which subsequently fuse to form myotubes. Direct damage to the basal lamina or expression of matrix metalloproteinase stimulated by nitric oxide release, may further release trapped growth factors in the extracellular matrix that encourage activation of MuSCs (Dimario et al, 1989; Tatsumi, 2010) These signals cause MuSCs to leave quiescence, migrate to the site of injury and begin proliferating. As many skeletal muscle pathologies are linked to a shift in the local metabolic environment (Chi et al, 1987; Joseph et al, 2018), and many metabolic disorders result in impaired skeletal muscle repair (D’Souza et al, 2016; Monaco et al, 2018), it is critical that we understand the link between MuSCs and their local tissue microenvironment

A LINK BETWEEN METABOLISM AND SKELETAL MUSCLE REGENERATION

CONCLUSION