A study recently published in Nature Biotechnology revealed a new technique to generate muscle fibers, thus offering a better model to study muscular diseases including Duchenne muscular dystrophy (DMD). During embryonic development, skeletal muscles arise from somites, which derive from the presomitic mesoderm (PSM). Using PSM development as a guide, the authors establish conditions for the differentiation of monolayer cultures of mouse embryonic stem (ES) cells into PSM-like cells without the introduction of transgenes or cell sorting. There is a significant need in the field to develop protocols for obtaining physiologically relevant skeletal muscle cells in order to effectively model muscle diseases. By applying their skeletal muscle differentiation protocol to mESCs derived from mdx mice, the authors were able to model aspects of DMD that have not previously been seen in vitro. They found that in vitro myotubes lacking dystrophin had increased lateral branching, consistent with myofiber splitting observed in some neuromuscular diseases. In muscle wasting diseases such as DMD, the endogenous satellite cells become exhausted over time and get replaced by fat and fibrotic tissue. The ability to generate an efficient protocol for producing skeletal muscle from PSCs provides a unique in vitro model to improve the understanding of the consequences of dystrophin loss in human skeletal muscle.
