Madeline B Searcy, Randolph K Larsen, Bradley T Stevens, Yang Zhang, Hongjian Jin, Catherine J Drummond, Casey G Langdon, Katherine E Gadek, Kyna Vuong, Kristin B Reed, Matthew R Garcia, Beisi Xu, Darden W Kimbrough, Grace E Adkins, Nadhir Djekidel, Shaina N Porter, Patrick A Schreiner, Shondra M Pruett-Miller, Brian J Abraham, Jerold E Rehg, Mark E Hatley
Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS. We show that P3F expression in aP2-Cre expressing cells reprograms endothelial progenitors to functional myogenic stem cells capable of regenerating injured muscle fibers...
November 15, 2023: Nature Communications