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Here we show that fibro\/adipogenic progenitors (FAPs) are a major cell-of-origin of HO in\u00a0an accurate genetic mouse model of FOP (\n                    <jats:italic>Acvr1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>tnR206H<\/jats:italic>\n                    <\/jats:sup>\n                    ). Targeted expression of the disease-causing type I bone morphogenetic protein (BMP) receptor, ACVR1(R206H), to FAPs recapitulates the full spectrum of HO observed in FOP patients. ACVR1(R206H)-expressing FAPs, but not wild-type FAPs, activate osteogenic signaling in response to activin ligands. Conditional loss of the wild-type\n                    <jats:italic>Acvr1<\/jats:italic>\n                    allele dramatically exacerbates FAP-directed HO, suggesting that mutant and wild-type ACVR1 receptor complexes compete for activin ligands or type II BMP receptor binding partners. Finally, systemic inhibition of activin A completely blocks HO and restores wild-type-like behavior to transplanted\n                    <jats:italic>Acvr1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>R206H\/+<\/jats:italic>\n                    <\/jats:sup>\n                    FAPs. Understanding the cells that drive HO may facilitate the development of cell-specific therapeutic approaches to inhibit catastrophic bone formation in FOP.\n                  <\/jats:p>","DOI":"10.1038\/s41467-018-02872-2","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T06:43:46Z","timestamp":1517208226000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":216,"title":["Activin-dependent signaling in fibro\/adipogenic progenitors causes fibrodysplasia ossificans progressiva"],"prefix":"10.1038","volume":"9","author":[{"given":"John B.","family":"Lees-Shepard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita A.","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J.","family":"Stoessel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah-Anne E.","family":"Nicholas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy A.","family":"Cogswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvathi M.","family":"Devarakonda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Michael J.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Cummins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Legendre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesa","family":"Kaartinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-8921","authenticated-orcid":false,"given":"David J.","family":"Goldhamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,2]]},"reference":[{"key":"2872_CR1","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ng1783","volume":"38","author":"EM Shore","year":"2006","unstructured":"Shore, E. 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