Defining the Skeletal Myogenic Lineage in Human Pluripotent Stem Cell-Derived Teratomas

Skeletal muscle stem cells are essential to muscle homeostasis and regeneration after in-jury, and have emerged as a promising cell source for treating skeletal disorders. An attractive ap-proach to obtain these cells utilizes differentiation of pluripotent stem cells (PSCs). We recently re-ported that teratomas derived from mouse PSCs are a rich source of skeletal muscle stem cells. Here, we showed that teratoma formation is also capable of producing skeletal myogenic progenitors from human PSCs. Using single-cell transcriptomics, we discovered several distinct skeletal myogenic subpopulations that represent progressive developmental stages of the skeletal myogenic lineage and recapitulate human embryonic skeletal myogenesis. We further discovered that ERBB3 and CD82 are effective surface markers for prospective isolation of the skeletal myogenic lineage in human PSC-derived teratomas. Therefore, teratoma formation provides an accessible model for ob-taining human skeletal myogenic progenitors from PSCs.