Satellite cells (SCs) are stem cells that lie under the basal lamina of muscle fibers and can regenerate muscle tissue following injury. Although these cells have been studied extensively in mouse and chicken embryos, little is known about human SCs and how these cells arise. Now, Olivier Pourquié and colleagues characterize the development of human skeletal muscle in vitro. They first generate human induced pluripotent stem cell (hiPSC) reporter lines that can be used to follow the expression of two key myogenic transcription factors – PAX7 and MYOG. Using these lines, the researchers first characterize the differentiation of hiPSCs into PAX7-positive myogenic precursors. Single cell RNA-seq analyses reveal that these PAX7-positive cells exhibit several characteristics of human fetal satellite cells. The researchers further show that these cells can differentiate into MYOG-positive myocytes that, in turn, are able to form myofibers in vitro. Finally, the authors demonstrate that, when transplanted into mice, hiPSC-derived PAX7-positive cells contribute to myofibers and are found under the basal lamina of myofibers, suggesting that they contribute to the SC pool. Overall, these findings provide important insights into the development of the human myogenic lineage and highlight that human satellite-like cells can be produced in vitro, opening up new avenues for regenerative therapies.
