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.