Several years ago, researchers at Massachusetts General Hospital (MGH) figured out a way to convert skin cells into muscle cells that were self-renewing and seemed promising for treating injuries and degenerative diseases like muscular dystrophy. But they weren’t quite sure how the conversion was happening.
Now they know—and they believe their insights could yield recipes for generating patient-matched muscle cells to treat a range of disorders.
The MGH researchers call their muscle cells myogenic progenitor cells (iMPCs). In a new study, published in the journal Genes & Development, they explain how adding three chemicals to skin cells causes them to transform into iMPCs.
A gene called MyoD can convert skin cells into muscle cells, but mature muscle cells cannot divide to create new muscle. In previous experiments, the researchers hit on three chemicals that could make skin cells revert to a stem-cell-like state instead, which would allow them to transform into self-renewing muscle cells.
The key, the MGH researchers discovered in the new study, is that the chemicals remove marks called methyl groups that are added to DNA in a process known as DNA methylation.
“DNA methylation typically maintains the identity of specialized cells, and we showed that its removal is key for acquiring a muscle stem cell identity,” said lead author Masaki Yagi, Ph.D., a research fellow at MGH, in a statement.
It’s the latest study focused on finding new ways to regenerate muscle. Earlier this year, an Australian team reported that a protein called NAMPT could regenerate muscle in zebrafish and mouse models by amplifying a natural healing process in the body that occurs when macrophages migrate to injury sites.
Other research groups have focused on the role of the MyoD protein in healing. A Sanford Burnham Prebys team, for example, discovered that in aging people, old muscle stem cells can trigger a DNA damage response that blocks MyoD and prevents muscle cells from forming.
The MGH scientists believe their findings could be useful beyond muscle regeneration. The three-chemical cocktail could be used to generate stem cells for a variety of tissue types, senior author Konrad Hochedlinger, Ph.D., a principal investigator at the Center for Regenerative Medicine at MGH and a professor of medicine at Harvard Medical School, said.
by Arlene Weintraub
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