Scientists have identified the mechanism behind the conversion of skin cells into immature muscle cells, which could lead to therapies preventing muscle degeneration.
In this
latest study, Hochedlinger and his colleagues uncovered the details behind how
this combination converts skin cells into iMPCs. They found that while MyoD
expression alone causes skin cells to take on the identity of mature muscle
cells, adding the three chemicals causes the skin cells to acquire a more
primitive stem cell-like state. Importantly, iMPCs are molecularly highly
similar to muscle tissue stem cells and muscle cells derived from iMPCs are
more stable and mature than muscle cells produced with MyoD expression alone.
“Mechanistically,
we showed that MyoD and the chemicals aid in the removal of certain marks on
DNA called DNA methylation,” said lead author Masaki Yagi. “DNA methylation
typically maintains the identity of specialised cells and we showed that its
removal is key for acquiring a muscle stem cell identity.”
Hochedlinger
believes that the findings may be applicable to other tissue types besides
muscle that involve different regulatory genes. Combining the expression of
these genes with the three chemicals used in this study could help researchers
generate different stem cell types that closely resemble a variety of tissues
in the body, potentially leading to new muscle-related disease treatments.
The
study was published in Genes & Development.
A team of researchers at the Massachusetts General Hospital (MGH), US, who previously developed a process for converting skin cells into immature muscle cells have uncovered how this process works and what molecular changes it triggers within cells. The research could allow clinicians to generate patient-matched muscle cells to help treat muscle injuries, age-related muscle degeneration or conditions such as muscular dystrophy.
The researchers previously found that expression of a muscle regulatory gene known as MyoD directly converts skin cells into mature muscle cells. However, mature muscle cells do not divide and self-renew and therefore they cannot be propagated for clinical purposes.
“To
address this shortcoming, we developed a system several years ago to convert
skin cells into self-renewing muscle stem-like cells we coined induced myogenic
progenitor cells (iMPCs). Our system uses MyoD in combination with three
chemicals we previously identified as facilitators of cell plasticity in other
contexts,” explained senior author Konrad Hochedlinger.