Meat Science and Muscle Biology Symposium: stem cell niche and postnatal muscle growth

Abstract

Stem cell niche plays a critical role in regulating the behavior and function of adult stem cells that underlie tissue growth, maintenance, and regeneration. In the skeletal muscle, stem cells, called satellite cells, contribute to postnatal muscle growth and hypertrophy, and thus, meat production in agricultural animals. Satellite cells are located adjacent to mature muscle fibers underneath a sheath of basal lamina. Microenvironmental signals from extracellular matrix mediated by the basal lamina and from the host myofiber both impinge on satellite cells to regulate their activity. Furthermore, several types of muscle interstitial cells, including intramuscular preadipocytes and connective tissue fibroblasts, have recently been shown to interact with satellite cells and actively regulate the growth and regeneration of postnatal skeletal muscles. From this regard, interstitial adipogenic cells are not only important for marbling and meat quality, but also represent an additional cellular component of the satellite cell niche. At the molecular level, these interstitial cells may interact with satellite cells through cell surface ligands, such as delta-like 1 homolog (Dlk1) protein whose overexpression is thought to be responsible for muscle hypertrophy in callipyge sheep. In fact, extracellular Dlk1 protein has been shown to promote the myogenic differentiation of satellite cells. Understanding the cellular and molecular mechanisms within the stem cell niche that regulate satellite cell differentiation and maintain muscle homeostasis may lead to promising approaches to optimizing muscle growth and composition, thus improving meat production and quality.

Figure 1

Panel A: cellular and molecular components of the muscle satellite cell (MuSC) niche. MuSC, including Pax7⁺Myf5⁻ and Pax7⁺Myf5⁺ cells that generated from asymmetrical cell division, are regulated by various growth factors. These mainly include IGF-1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB), and vascular endothelial growth factor (VEGF). The physical and cellular components of MuSC niche include basal lamina, host myofiber, interstitial fibroblasts (transcriptional factor 4 positive cells, Tcf4⁺), preadipocytes (Pax3⁻/Myf5⁻), and vasculature. Other muscle resident stem cell types (Pw1⁺/Pax7⁻ PIC, CD133⁺ cell, mesoangioblast, pericyte, bone marrow-derived cell, BMDC) may interact with or give rise to MuSC. Panel B: regulation of MuSC fate choices by cues present in the niche. Signals from resting muscle inhibit the expansion of interstitial cells, including preadipocytes and fibroblasts, whereas cues from regenerating muscle promote proliferation of interstitial cells. During muscle regeneration, interstitial cells may provide physical and chemical cues [e.g., delta-like 1 homolog (Dlk1) and IL-6] that facilitate myogenic differentiation. Pax3/7: paired box 3/7; Myf5: myogenic factor 5; PIC: Pw1 (paternally expressed 3) positive interstitial cells. Color version available in the online PDF.