New tools for dissecting muscle stem cell function
Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibers that contract to generate force in a controlled and directed manner. Skeletal muscle is first formed during embryogenesis from a subset of muscle precursor cells found in a region of the embryo known as the myotome. In addition to generating differentiated muscle fibers, these cells also give rise to specialized muscle-forming stem cells, which remain associated with muscle fibers and are responsible for muscle
growth and repair throughout life. My lab was the first to develop cell sorting technologies to enable the direct purification of these rare muscle stem cells from adult muscle tissue. We have shown in mice that these cells can be used to regenerate diseased muscle tissue and that their loss during aging contributes to age-associated muscle weakness. Thus, muscle stem cells are promising targets for cell therapies involving either cell replacement or activation of endogenous repair mechanisms. However, little is known about the molecular pathways that regulate either the formation or the function of muscle stem cells. Thus, the goal of the studies proposed here is to exploit the power of stem cell biology to develop scalable assay systems for high-throughput screening of chemical modifiers of muscle stem cell formation, expansion, differentiation and survival, and to use these assays in a proof-of-principle screen to discover novel kinase pathways that are involved in muscle formation. The insights gained from these studies will have far-reaching consequences both for our basic understanding of tissue specification and ultimately in achieving effective treatments for muscle degenerative disease.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.