Fibroblast muscles
A new understanding of the mechanism that can help in the treatment of muscle-related diseases
Anna Yudina, "Scientific Russia"
Scientists who have developed the process of converting skin cells into immature muscle cells report the molecular changes it causes, according to a press release from New insights on mechanism that could help treat muscle-related diseases.
Researchers who previously developed a recipe for turning skin cells into primitive muscle-like cells that can be maintained in the laboratory for an unlimited time without losing the ability to become mature muscles have now revealed how this recipe works and what molecular changes it causes in cells. A study conducted by scientists from Massachusetts General Hospital (MGH) and published in the journal Genes&Development (Yagi et al., Dissecting dual roles of MyoD during lineage conversion to mature myocytes and myogenic stem cells). Its results may allow doctors to create muscle cells suitable for the patient to treat injuries associated with muscle aging or conditions such as muscle failure or dystrophy.
It is known that the expression of the MyoD muscle regulating gene is sufficient for the direct conversion of skin cells into mature muscle cells; however, mature muscle cells do not divide or renew, so they cannot be multiplied for clinical purposes. "To eliminate this shortcoming, a few years ago we developed a system for converting skin cells into self–renewing muscle stem cells - induced myogenic progenitor cells, or iMPC. Our system uses MyoD in combination with three chemicals that we have previously identified as promoting cellular plasticity in other contexts," explains senior author Konrad Hochedlinger, PhD, principal investigator at the MGH Center for Regenerative Medicine and professor of medicine at Harvard Medical School.
In this latest study, Hochedlinger and his colleagues revealed the details of how this combination turns skin cells into iMPC. They found that while the expression of MyoD itself causes skin cells to acquire the identity of mature muscle cells, the addition of three chemicals causes skin cells to instead acquire a more primitive stem cell-like state. It is important to note that impcs are very similar to muscle tissue stem cells, and muscle cells derived from iMPC are more stable and mature than muscle cells obtained with MyoD expression alone. "Mechanically, we have shown that MyoD and chemicals help in removing certain tags on DNA and disabling DNA methylation," says lead author Masaki Yagi, PhD, a researcher at MGH. "DNA methylation usually maintains the identity of specialized cells, and we have shown that its removal is the key to obtaining the identity of muscle stem cells."
Hochedlinger notes that the results may be applicable to other types of tissues besides muscles, which include other regulatory genes. Combining the expression of these genes with the three chemicals used in this study could help researchers generate different types of stem cells that are very similar to different tissues in the body.
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