RRC ID 49256
Author Ito N, Kii I, Shimizu N, Tanaka H, Takeda S.
Title Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells.
Journal Sci Rep
Abstract 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.
Volume 7(1)
Pages 8097
Published 2017-8-14
DOI 10.1038/s41598-017-08232-2
PII 10.1038/s41598-017-08232-2
PMID 28808339
PMC PMC5556026
MeSH Animals Cell Differentiation / physiology Cells, Cultured Dystrophin / metabolism Fibroblasts / metabolism Fibroblasts / physiology* Male Mice Mice, Inbred C57BL Muscle, Skeletal / metabolism Muscle, Skeletal / physiology* Muscular Dystrophy, Duchenne / metabolism Muscular Dystrophy, Duchenne / physiopathology Satellite Cells, Skeletal Muscle / metabolism Satellite Cells, Skeletal Muscle / physiology* Stem Cells / metabolism Stem Cells / physiology* Transcription Factors / metabolism*
IF 3.998
Times Cited 10
DNA material CSIV-TRE-RfA-CMV-KT (RDB12876) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393).