Satellite cells, which are muscle stem cells, have important roles in postnatal muscle growth and in adult muscle regeneration. Muscle injury activates the satellite cells in adult muscle but, interestingly, although most activated satellite cells divide rapidly, a few divide slowly. Now, on page , Yusuke Ono and colleagues suggest that only the slowly dividing satellite cells retain long-term self-renewal ability. The authors isolate satellite cells from adult mouse muscle, label them with the lipophilic dye PKH26, stimulate them to divide and sort them into PKH26low fast-dividing cells and PKHhigh slow-dividing cells. Fast-dividing cells generate more differentiated and self-renewing cells than slow-dividing cells, report the authors. However, slow-dividing cells form secondary myogenic colonies when passaged, whereas fast-dividing cells rapidly undergo myogenic differentiate without producing self-renewing cells. Notably, when transplanted into an injured muscle, slow-dividing cells contribute extensivelytomuscleregeneration. The authors also report that only those slow-dividing cells that express high levels of Id1 (a negative regulator of bHLH transcription factors) retain long-term self-renewal activity. Thus, they conclude, undifferentiated slow-dividing satellite cells retain ‘stemness’ and therefore might be essential for muscle homeostasis throughout life.
