Year 3

Stem cell therapies are poised to transform the way medicine is delivered to patients with diseases for which currently no treatment exists, such as muscle wasting due to injury, disease, and aging. Muscle stem cells (MuSCs) are indispensable for muscle regeneration and could meet the need to treat muscle wasting alleviating the disease burden and burgeoning healthcare costs in California associated with living longer. While adult MuSCs have potent self-renewal and regenerative potential, the MuSC population becomes increasingly heterogeneous and dysfunctional with aging.

The approach developed here provides a new tool for identifying and isolating myogenic progenitors in murine and human muscle biopsies via the single-cell mass cytometry (CyTOF) technology.  The simultaneous analyses of multiple cell surface markers and intracellular targets in well-defined populations can be performed and therefore provides the unprecedented way to characterize cellular signals that control stem cell functions.  We have identified specific markers, validated reagents and methods for CyTOF analysis of muscle stem and progenitor cells in mouse and human skeletal muscle tissue.  In particular, we have developed 50 metal-conjugated antibodies that allow us to uncover different populations of muscle cells and identify a potent stem cell population that robustly responses to specific niche signaling factors to enhance muscle repair during injury.  In summary, our approach sets the stage for investigating the cellular and molecular defects that characterize aging and muscle diseases and opens the door to the discovery of novel therapeutic targets to improve muscle regeneration.