Potential myoblasts hide out in the intestine.

Gerhart et al. report that stably committed muscle stem cells may wait in a quiescent state in mature nonmuscle tissues like brain and liver, retaining the ability to differentiate into skeletal muscle if the opportunity arises (page 381). This discovery may provide both an important tool for developing regenerative therapies, and a challenge to the characterization of some stem cells as multipotential, an idea based on reported conversions of one cell type to another. Some of the conversion experiments were performed with nonclonal cell populations. The current work suggests that the varied phenotypes observed in the earlier experiments may have arisen from a heterogeneous population of mature stem cells committed to different lineages.

The authors found scattered cells expressing MyoD, a marker for skeletal muscle precursors, in a wide variety of fully differentiated organs in chicken fetuses. When cultured in vitro, some cells from the fetal organs gave rise to skeletal muscle, and when the MyoD-positive cells were isolated by fluorescence activated cell sorting, almost all were able to form skeletal muscle. The cells resemble skeletal myoblasts, and appear to be stem cells stably committed to forming muscle. Previous work suggests that some cells in the neuronal tissues of mice also express muscle-specific transcription factors, and Gerhart et al. believe that stably committed precursors of other lineages may also be distributed in mature organs.Although the evolutionary utility of having muscle stem cells in nonmuscle tissues is not immediately obvious, one possibility is that they could be recruited to help the embryo recover from a loss of somite tissue. Medically, the presence of these cells may explain the origins of rhabdomyosarcomas, malignant tumors that express skeletal muscle proteins but often arise in nonmuscle tissue. Because these cells are stably committed to a specific lineage, they might also be useful for regenerative therapies, particularly if they are able to induce multipotential stem cells to differentiate in damaged tissue. ▪