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Heterotopic ossification (HO) is tightly linked to vascularization with increased vessel number in hereditary forms of HO, such as\n                    <jats:italic>Fibrodysplasia ossificans progressiva<\/jats:italic>\n                    (FOP). FOP is caused by mutations in the BMP type I receptor\n                    <jats:italic>ACVR1<\/jats:italic>\n                    leading to aberrant SMAD1\/5 signaling in response to ActivinA. Whether observed vascular phenotype in human FOP lesions is connected to aberrant ActivinA signaling is unknown. Blocking of ActivinA prevents HO in FOP mice indicating a central role of the ligand in FOP. Here, we established a new FOP endothelial cell model generated from induced pluripotent stem cells (iECs) to study ActivinA signaling. FOP iECs recapitulate pathogenic ActivinA\/SMAD1\/5 signaling. Whole transcriptome analysis identified ActivinA mediated activation of the BMP\/NOTCH pathway exclusively in FOP iECs, which was rescued to WT transcriptional levels by the drug candidate Saracatinib. We propose that ActivinA causes transcriptional pre-patterning of the FOP endothelium, which might contribute to differential vascularity in FOP lesions compared to non-hereditary HO.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s12015-020-10103-9","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T22:03:16Z","timestamp":1609970596000},"page":"1039-1052","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["ActivinA Induced SMAD1\/5 Signaling in an iPSC Derived EC Model of Fibrodysplasia Ossificans Progressiva (FOP) Can Be Rescued by the Drug Candidate Saracatinib"],"prefix":"10.1007","volume":"17","author":[{"given":"Susanne","family":"Hildebrandt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Kampfrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hildebrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Haupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Stachelscheid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2492-1667","authenticated-orcid":false,"given":"Petra","family":"Knaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"issue":"6","key":"10103_CR1","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1042\/BST20140231","volume":"42","author":"Y Jin","year":"2014","unstructured":"Jin, Y., Kaluza, D., & Jakobsson, L. (2014). VEGF, notch and TGF\u03b2\/BMPs in regulation of sprouting angiogenesis and vascular patterning. Biochemical Society Transactions, 42(6), 1576\u20131583. https:\/\/doi.org\/10.1042\/BST20140231.","journal-title":"Biochemical Society Transactions"},{"issue":"7","key":"10103_CR2","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrc2868","volume":"10","author":"AS Chung","year":"2010","unstructured":"Chung, A. S., Lee, J., & Ferrara, N. (2010). Targeting the tumour vasculature: Insights from physiological angiogenesis. Nature Reviews Cancer, 10(7), 505\u2013514. https:\/\/doi.org\/10.1038\/nrc2868.","journal-title":"Nature Reviews Cancer"},{"issue":"4","key":"10103_CR3","doi-asserted-by":"publisher","first-page":"e10172","DOI":"10.1002\/jbm4.10172","volume":"3","author":"C Meyers","year":"2019","unstructured":"Meyers, C., Lisiecki, J., Miller, S., Levin, A., Fayad, L., Ding, C., Sono, T., McCarthy, E., Levi, B., & James, A. W. (2019). 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