Molecular regulation of determination in asymmetrically dividing muscle stem cells

Asymmetric cell division is a conserved mechanism to generate progeny with divergent fates. In the context of somatic stem cells, it provides a mode of selfrenewal that retains the stem cell identity of one daughter cell while producing another daughter cell that is committed to differentiation. This allows for a balance between the requirement for committed progenitors during regeneration and the maintenance of tissue stem cells. Recently, skeletal muscle stem cells have stepped into the spotlight as a tractable paradigm to study the molecular determinants regulating asymmetric stem cell divisions. By examining this system, a recent study has yielded important insight into the molecular mechanisms that lead to the distinct identities of stem cell progeny. Muscle regeneration depends on the participation of a heterogeneous population of stem cells and progenitors known as satellite cells. The satellite stem cell population, which is marked by the absence of expression of the myogenic regulatory factor (MRF) Myf5, is able to resist differentiation and maintain the satellite cell compartment after regeneration; on the other hand, committed satellite myogenic cells, which express the MRFs Myf5 and MyoD, are the predominant cell type that differentiates and fuses into myofibers. While Myf5 satellite stem cells can asymmetrically divide to give rise to Myf5 satellite myogenic cells, other modes of asymmetric divisions have been observed in myoblasts, which give rise to either MyoD reserve cells or Pax7/MyoG differentiating myocytes. Although these modes of divisions are distinct from asymmetric satellite stem cell divisions, there are likely overlapping fate determinants, Molecular regulation of determination in asymmetrically dividing muscle stem cells