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Updated: May 1, 2026
Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
Dedifferentiation of mammalian myotubes induced by msx1
S J Odelberg1, A Kollhoff, M T Keating
1Division of Cardiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA. odelberg@howard.genetics.utah.edu
Abstract:
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.
Insights
Terminally differentiated mammalian cells, previously thought irreversible, can dedifferentiate. Ectopic msx1 expression in murine myotubes induced dedifferentiation, enabling redifferentiation into multiple cell types.
Area of Science:
- Cell Biology
- Developmental Biology
- Muscle Stem Cell Research
Background:
- Cellular differentiation is generally considered a terminal and irreversible process in mammals.
- Terminally differentiated cells maintain specialized functions but lose proliferative potential.
Purpose of the Study:
- To investigate the potential for terminally differentiated mammalian myotubes to dedifferentiate.
- To explore the role of msx1 in initiating the dedifferentiation of myotubes.
Main Methods:
- Utilized C2C12 murine myotubes as a model system.
- Induced ectopic expression of the msx1 gene.
- Assessed changes in muscle-specific proteins (MyoD, myogenin, MRF4, p21).
- Analyzed cell morphology, proliferation, and clonal populations.
Main Results:
- Ectopic msx1 expression reduced key muscle proteins in 20%-50% of myotubes.
- Approximately 9% of myotubes underwent cleavage, forming smaller myotubes or proliferating mononucleated cells.
- Derived mononucleated cells could be redifferentiated into chondrogenic, adipogenic, myogenic, and osteogenic lineages.
Conclusions:
- Terminally differentiated mammalian myotubes can dedifferentiate upon appropriate stimulation.
- Msx1 plays a role in facilitating this myotube dedifferentiation process.
- Dedifferentiated cells retain multipotency, suggesting plasticity in terminally differentiated cells.
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