Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells

• Published in: Scientific reports Vol. 7; no. 1; pp. 8097 - 12
• Main Authors: Ito, Naoki, Kii, Isao, Shimizu, Noriaki, Tanaka, Hirotoshi, Takeda, Shin'ichi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 14.08.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Calcein; Cell Differentiation - physiology; Cells, Cultured; Duchenne's muscular dystrophy; Dystrophin; Dystrophin - metabolism; Embryo fibroblasts; Embryos; Esterase; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - physiology; Gene expression; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - physiopathology; Musculoskeletal system; MyoD protein; Pax3 protein; Rodents; Satellite cells; Satellite Cells, Skeletal Muscle - metabolism; Satellite Cells, Skeletal Muscle - physiology; Skeletal muscle; Stem cell transplantation; Stem cells; Stem Cells - metabolism; Stem Cells - physiology; Transcription factors; Transcription Factors - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-08232-2

Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Gene expression analysis of this subpopulation revealed that defined combinations of transcription factors (Pax3, Mef2b, and Pitx1 or Pax7, Mef2b, and Pitx1 in embryonic fibroblasts, and Pax7, Mef2b and MyoD in adult fibroblasts) reprogrammed fibroblasts into skeletal muscle progenitor cells. These reprogrammed cells formed Dystrophin-positive mature muscle fibers when transplanted into a mouse model of Duchenne muscular dystrophy. These results highlight the new marker for heterogenous population of cultured satellite cells, potential therapeutic approaches and cell sources for degenerative muscle diseases.