Persistent expression of MNF identifies myogenic stem cells in postnatal muscles.
Skeletal muscles contain an undifferentiated myogenic stem cell pool (satellite cells) that can be mobilized to regenerate myofibers in response to injury. We have determined that the winged helix transcription factor MNF is expressed selectively in quiescent satellite cells, which do not express known regulators of the myogenic program. Following muscle injury, MNF is present transiently in proliferating satellite cells and in centralized nuclei of regenerating myofibers, but expression declines as these fibers mature, until only the residual stem cell pool continues to express detectable levels of MNF. MNF also is expressed selectively but transiently at embryonic stages of myogenesis in the developing myotome, limb bud precursors, and heart tube, but by late fetal stages of development, MNF is down-regulated within differentiated cardiac and skeletal myocytes, and persistently high expression is observed only in satellite cells. These data identify MNF as a marker of quiescent satellite cells and suggest that downstream genes controlled by MNF serve to modulate proliferative growth or differentiation in this unique cell population.
Garry
D J
DJ
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA.
Yang
Q
Q
Bassel-Duby
R
R
Williams
R S
RS
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D005314:Embryonic and Fetal Development; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D018878:Limb Buds / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009124:Muscle Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D051787:Myogenic Regulatory Factor 5; D016133:Polymerase Chain Reaction; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D015534:Trans-Activators; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*
D015415:Biomarkers; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C497672:Foxk1 protein, mouse; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D015534:Trans-Activators; D014157:Transcription Factors