Followed by refreshments in the WTB Atrium
Skeletal muscles of the body arise from segmented embryonic structures called somites. The segmental or metameric organization of somites is established early in embryogenesis when pairs of embryonic segments are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock. While this oscillator has been well characterized in model organisms, whether a similar oscillator exists in humans remains unknown. We have previously shown that human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells can differentiate in vitro into PSM upon activation of the Wnt signaling pathway combined with BMP inhibition. We show that these human PSM cells exhibit Notch and YAP-dependent oscillations of the cyclic gene HES7 with a 5-hour period. Single cell RNA-sequencing comparison of the differentiating iPS cells with mouse PSM reveals that human PSM cells follow a similar differentiation path and exhibit a remarkably coordinated differentiation sequence. When these PSM-like cells are allowed to develop further in vitro, they produce striated, millimeter-long muscle fibers together with satellite-like cells. I will present the cellular and molecular characterization and the regenerative potential of these human PAX7+ satellite-like cells produced in vitro. We have also used human isogenic iPS lines differentiated to a myogenic fate to establish an in vitro model of Duchenne Muscular Dystrophy recapitulating several key features of this pathology.