Cell Atlas of Muscle Regeneration Compiled

Muscle repair is complicated. In order to regenerate tissue, numerous cell types have to coordinate with each other. In a study published today in Cell Reports, researchers used a new cellular profiling technology to probe and catalog the activity of almost every kind of cell involved in muscle repair.

The researchers profiled approximately 35,000 individual cells and compiled their findings into a “cell atlas” of muscle regeneration. This resource provides a comprehensive picture of the many intricate cellular interactions in tissue self-repair and may potentially lead to better rehabilitation strategies and support for patients recovering from muscle injuries.

To get their data, the researchers used single-cell RNA sequencing to analyze the gene expression signatures of individual cells, all taken from the actively regenerating muscles of mice—including the rare muscle stem cells that drive the repair process. They then applied new algorithms to filter the extensive collection of molecular information.

“Because we have such a large dataset, it helps us frame a number of hypothesis-driven questions about not only which cells are involved but how they are communicating with each other,” says senior author Ben Cosgrove of Cornell University.

Unlike a road atlas that uses spatial coordinates, this atlas is more of a “laundry list of the key cell players,” Cosgrove says, itemizing their similarities and differences with 15 unique cell types in muscle tissue. This collection emphasizes how much heterogeneity exists within each cell type, a range of diversity that led the researchers to pursue the sources of specific molecular variations that might be otherwise overlooked.

The researchers have already used the atlas to identify the role a class of proteins called syndecans play in enabling muscle stem cells to make a binary choice during muscle regeneration. As stem cells divide, they choose either to replenish the stem cell population or else to turn into the mature myofiber cells that replace damaged muscle tissue.

“We took this huge atlas and partitioned it down to the stem cells. And then we organized the stem cells in a way that gives us a framework to think about variation and the choices the cells are making,” Cosgrove says. Their findings show that syndecan-related variations may help direct how muscle stem cells respond to signals from their neighboring cells and which outcome they choose.

The researchers are currently applying this approach to look at muscle repair deficiency in aging and muscular dystrophy.