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Here, we use fibrodysplasia ossificans progressiva (FOP), a disease of progressive HO caused by\n                    <jats:italic>ACVR1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>R206H<\/jats:italic>\n                    <\/jats:sup>\n                    (Activin receptor type-1 receptor) mutation, to elucidate how ACVR1 affects skeletal muscle repair. Rare and unique primary FOP human muscle stem cells (Hu-MuSCs) isolated from cadaveric skeletal muscle demonstrated increased extracellular matric (ECM) marker expression, showed skeletal muscle-specific impaired engraftment and regeneration ability. Human induced pluripotent stem cell (iPSC)-derived muscle stem\/progenitor cells (iMPCs) single-cell transcriptome analyses from FOP also revealed unusually increased ECM and osteogenic marker expression compared to control iMPCs. These results show that iMPCs can recapitulate many aspects of Hu-MuSCs for detailed in vitro study; that ACVR1 is a key regulator of Hu-MuSC function and skeletal muscle repair; and that ACVR1 activation in iMPCs or Hu-MuSCs may contribute to HO by changing the local tissue environment.\n                  <\/jats:p>","DOI":"10.7554\/elife.66107","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T07:15:15Z","timestamp":1636528515000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.66107","source":"Crossref","is-referenced-by-count":6,"title":["Modeling the ACVR1R206H mutation in human skeletal muscle stem cells"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-024X","authenticated-orcid":true,"given":"Emilie","family":"Barruet","sequence":"first","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Departments of Surgery and Orofacial Sciences, the Program in Craniofacial Biology, and 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