Dedifferentiation of mammalian myotubes induced by msx1.
The process of cellular differentiation culminating in terminally differentiated mammalian cells is thought to be irreversible. Here, we present evidence that terminally differentiated murine myotubes can be induced to dedifferentiate. Ectopic expression of msx1 in C2C12 myotubes reduced the nuclear muscle proteins MyoD, myogenin, MRF4, and p21 to undetectable levels in 20%-50% of the myotubes. Approximately 9% of the myotubes cleave to produce either smaller multinucleated myotubes or proliferating, mononucleated cells. Finally, clonal populations of the myotube-derived mononucleated cells can be induced to redifferentiate into cells expressing chondrogenic, adipogenic, myogenic, and osteogenic markers. These results suggest that terminally differentiated mammalian myotubes can dedifferentiate when stimulated with the appropriate signals and that msx1 can contribute to the dedifferentiation process.
Odelberg
S J
SJ
Division of Cardiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA. odelberg@howard.genetics.utah.edu
Kollhoff
A
A
Keating
M T
MT
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002999:Clone Cells; D015870:Gene Expression / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D051957:MSX1 Transcription Factor; D008322:Mammals; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D009124:Muscle Proteins; D014157:Transcription Factors