Heterogeneity in the muscle satellite cell population

Abstract

Satellite cells, the adult stem cells responsible for skeletal muscle regeneration, are defined by their location between the basal lamina and the fiber sarcolemma. Increasing evidence suggests that satellite cells represent a heterogeneous population of cells with distinct embryological origin and multiple levels of biochemical and functional diversity. This review focuses on the rich diversity of the satellite cell population based on studies across species. Ultimately, a more complete characterization of the heterogeneity of satellite cells will be essential to understand the functional significance in terms of muscle growth, homeostasis, tissue repair, and aging.

Figure 1. Schematic representation of SC myogenic progression

Upon activation, SCs (initially Pax7+/MyoD−) can enter the myogenic program by either inducing Myf5 or MyoD expression. Most of the cells subsequently express both determination genes and terminally differentiate by inducing Myogenin (Mgn+) expression and then fusing to form multinucleated fibers. A fraction of the SCs self-renew by down-regulating MyoD. Dashed lines represent possible but not proven connections. A fraction of SCs possibly differentiate without entering the cell cycle (see text). The newly formed fiber on the right is depicted as having centrally placed nuclei to reflect the process that occurs during muscle regeneration as opposed to homeostatic turnover of mature myonuclei by SCs which occurs normally at a very low level.