Neurogenic heterotopic ossifications (NHO) are frequent complications of traumatic brain and spinal cord injuries (SCI). NHO are abnormal ossifications within periarticular muscles resulting in joint ankylosis, vessel and nerve compression. To elucidate NHO pathogenesis, we have developed the first mouse model of SCI-induced NHO, in which NHO is induced in cardiotoxin-injured muscle only when following a SCI in genetically unmanipulated mice. However, what stem cell populations within muscles differentiate into osteoblasts to directly form NHO is unclear. We hypothesized that injured muscles do not repair normally after SCI, and instead osteogenic differentiation of skeletal muscle-resident stem cells takes place. We focused on the two progenitor populations known to reside within skeletal muscles: satellite cells (SCs) and fibro- adipogenic progenitors (FAPs). SCs, which specifically express the transcription factor Pax7, differentiate into myoblasts whereas FAPs, which express instead the transcription factor Prrx1 and are of mesenchymal origin, can differentiate into fibroblasts and adipocytes in vitro. We have previously shown that both populations can deposit mineralised calcium under osteogenic condition in vitro. We have now generated Pax7CreER x R26-ZsGreen (Pax7ZsG) and Prrx1Cre x R26-ZsGreen (Prrx1ZsG) to specifically trace the fate of SCs and FAPs respectively in our SCI-induced NHO model in vivo. We demonstrate that after SCI, Pax7+ SCs fail to proliferate and regenerate myofibers in injured muscles with instead persistent proliferation of Prrx1+ FAPs differentiating into osteocalcin+ osteoblasts in SCI-NHO at 21 days post-surgery. This suggests that SCI causes muscle repair failure with instead proliferation and osteogenic differentiation of FAPs residing in the muscle. In addition, SCI significantly upregulated platelet-derived growth factor receptor (PDGFR) expression in FAPs in skeletal muscles indicating that dysregulation of PDGFR signalling may be involved in NHO development.