Pluripotent stem cells have the capacity to differentiate into many types of cell lineages including skeletal myocytes. Nevertheless, the frequency of pluripotent stem cells generating skeletal myocytes in the absence of developmental cues is very low, and signaling molecules are required to commit them to muscle lineage. Thereby, in vitro stem cell differentiation has been used for decades to study molecular mechanisms of myogenic specification. Similar to human embryonic stem (ES) cells, various mouse pluripotent stem cells respond well to development cues in vitro to differentiate into cell types of all three primary germ layers. In tissue cultures, they can be induced into myogenic differentiation with an aggregation protocol which involves the formation of embryoid bodies (EBs). Their commitment into the skeletal muscle lineage recapitulates closely the cellular and molecular processes occurring in the early embryogenesis. Treatment of these stem cells with regulatory signals important for embryonic development, such as ligands of nuclear receptors, during EB formation markedly enhances the efficiency of myogenic differentiation. However, many challenges remain. Understanding on a molecular level, how different signaling pathways and chromatin dynamics converge during stem cell differentiation to specify the muscle lineage is imperative for identifying effective signaling molecules to generate sufficient amount of muscle progenitor cells for potential therapeutics. To this end, mouse stem cells will continue to serve as valuable model systems due to their close resemblance to skeletal myogenesis in vivo, and the ease of manipulation in experimental procedures. In this chapter, we will focus on recent research findings on nuclear receptor signaling in the specification of skeletal muscle lineage.
Part of the book: Pluripotent Stem Cells