DMD: How muscle cells journey to the dark side

Scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) have revealed that FAPs don’t have just one identity—but several distinct identities that emerge during key stages of muscle regeneration. Importantly, the FAPs that drive the symptoms of Duchenne Muscular Dystrophy have defined markers, meaning they could be targeted for drug development.

The study was published in Nature Communications.

Puri’s team analyzed the transcriptome of single FAP cells, which shows the genes that are turned on or off, from samples of muscle tissue obtained from mouse models of acute injury and DMD. This work identified cellular markers unique to a subpopulation of FAPs (sub-FAPs).

The scientists then applied the transcriptome analysis to each of the identified sub-FAPs to track the relative amounts of gene expression and types of genes expressed in three settings of muscle regeneration: following acute injury; during DMD; and immediately after birth, which uses a different regeneration process from adult muscle repair.

Clear patterns emerged and revealed that the identified sub-FAPs transitioned through different functional states—correlating with key events during the muscle regeneration process. At early stages after acute injury, sub-FAPs expressing the cell surface marker Tie2 appear. They were followed by transient sub-FAPs expressing the cell surface marker Vcam1. Genome-wide transcriptome analysis indicated that Tie2-expressing FAPs promote blood vessel formation and muscle stem cell activation, while Vcam1-expressing sub-FAPs promote fibrosis.

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Liz Andersson

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