Self-renewal of the adult skeletal muscle satellite cell

Abstract

The concept of the stem cell has evolved in dynamic systems such as those involved in embryonic development and, in the adult, in tissues such as blood and skin which are continuously renewed. It has proved difficult to establish whether stem cell mechanisms underlie the maintenance of the more stable tissues that form the majority of the adult body. We have investigated skeletal muscle, a low-turnover and largely postmitotic tissue which nevertheless maintains a remarkable capacity to regenerate itself following injury. The contractile units of muscle are myofibers, elongated syncytial cells each containing many hundreds of postmitotic myonuclei. Satellite cells are resident beneath the basal lamina of myofibers and function as myogenic precursors during muscle regeneration. We have recently demonstrated that as few as seven Pax7(+) satellite cells associated with one myofiber can regenerate a hundred or more new myofibers containing thousands of myonuclei. Satellite cells also undergo self-renewal, giving them the ability to participate in multiple rounds of injury-induced regeneration. The satellite cell may thus serve as a prototype for stem cell function in stable adult tissues: a tissue-specific progenitor which is normally quiescent but which has self-renewal properties similar to those of better known stem cells.