Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by 
progressive ossification of soft tissues, for which there is no effective 
treatment. Mutations in the bone morphogenetic protein (BMP) type I receptor 
activin receptor-like kinase 2 (ACVR1/ALK2) are the main cause of FOP. We 
generated human induced pluripotent stem cells (hiPSCs) from FOP patients with 
the ALK2 R206H mutation. The mutant ALK2 gene changed differentiation 
efficiencies of hiPSCs into FOP bone-forming progenitors: endothelial cells 
(ECs) and pericytes. ECs from FOP hiPSCs showed reduced expression of vascular 
endothelial growth factor receptor 2 and could transform into mesenchymal cells 
through endothelial-mesenchymal transition. Increased mineralization of 
pericytes from FOP hiPSCs could be partly inhibited by the ALK2 kinase inhibitor 
LDN-212854. Thus, differentiated FOP hiPSCs recapitulate some aspects of the 
disease phenotype in vitro, and they could be instrumental in further 
elucidating underlying mechanisms of FOP and development of therapeutic drug 
candidates.