Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury.
Adult bone marrow-derived cells (BMDC) are shown to contribute to muscle tissue in a step-wise biological progression. Following irradiation-induced damage, transplanted GFP-labeled BMDC become satellite cells: membrane-ensheathed mononucleate muscle stem cells. Following a subsequent exercise-induced damage, GFP-labeled multinucleate myofibers are detected. Isolated GFP-labeled satellite cells are heritably myogenic. They express three characteristic muscle markers, are karyotypically diploid, and form clones that can fuse into multinucleate cells in culture or into myofibers after injection into mouse muscles. These results suggest that two temporally distinct injury-related signals first induce BMDC to occupy the muscle stem cell niche and then to help regenerate mature muscle fibers. The stress-induced progression of BMDC to muscle satellite cell to muscle fiber results in a contribution to as many as 3.5% of muscle fibers and is due to developmental plasticity in response to environmental cues.
LaBarge
Mark A
MA
Baxter Laboratory for Genetic Pharmacology, Department of Microbiology and Immunology, Department of Molecular Pharmacology, Stanford University School of Medicine, CCSR 4215, Stanford, CA 94305, USA.
Blau
Helen M
HM
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries / Q000502:physiology; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D012420:Running / Q000293:injuries; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins