Pax7 is necessary and sufficient for the myogenic specification of CD45+:Sca1+ stem cells from injured muscle.
CD45(+):Sca1(+) adult stem cells isolated from uninjured muscle do not display any myogenic potential, whereas those isolated from regenerating muscle give rise to myoblasts expressing the paired-box transcription factor Pax7 and the bHLH factors Myf5 and MyoD. By contrast, CD45(+):Sca1(+) isolated from injured Pax7( -/-) muscle were incapable of forming myoblasts. Infection of CD45(+):Sca1(+) cells from uninjured muscle with retrovirus expressing Pax7 efficiently activated the myogenic program. The resulting myoblasts expressed Myf5 and MyoD and differentiated into myotubes that expressed myogenin and myosin heavy chain. Infection of CD45(-):Sca1(-) cells from Pax7( -/-) muscle similarly gave rise to myoblasts. Notably, infection of Pax7-deficient muscle with adenoviral Pax7 resulted in the de novo formation of regenerated myofibers. Taken together, these results indicate that Pax7 is necessary and sufficient to induce the myogenic specification of CD45(+) stem cells resident in adult skeletal muscle. Moreover, these experiments suggest that viral transduction of Pax7 is a potential therapeutic approach for the treatment of neuromuscular degenerative diseases.
Seale
Patrick
P
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Ishibashi
Jeff
J
Scimè
Anthony
A
Rudnicki
Michael A
MA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002469:Cell Separation; D017690:Cell Transplantation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000096:biosynthesis; D018995:Myosin Heavy Chains / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D012038:Regeneration; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D014157:Transcription Factors; D017493:Leukocyte Common Antigens; D018995:Myosin Heavy Chains