Deconstructing human somitogenesis in vitro

Olivier Pourquié, Department of Genetics, Harvard Medical School and Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA / Harvard Stem Cell Institute, Harvard University, Cambridge, MA USA

Abstract: The spine is characterized by the periodic arrangement of vertebrae along the anterior-posterior (AP) axis. This segmental or metameric organization is established early in embryogenesis when pairs of embryonic segments called somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock. The segmentation clock generates a complex signaling pulse of Notch, Wnt and FGF activity involved in the rhythmic production of somites. This oscillator has been well characterized in model organisms, where it has been shown to tick with a species-specific period.

Virtually nothing is known on human somitogenesis as it proceeds between 3- and 4-weeks post conception when embryos are extremely difficult to access. We have developed protocols to differentiate human pluripotent stem cells (ES/iPS) in vitro into PSM cells. Single cell RNA-sequencing comparison of these human cells differentiating in vitro with mouse embryo PSM reveals that they faithfully recapitulate the PSM differentiation sequence in vitro. Using our in vitro system as a proxy for human somitogenesis, we were able to demonstrate that human iPS reporter cells harboring a HES7 fluorescent reporter differentiated to PSM exhibit 5-hour oscillations, thus identifying the human segmentation clock. These novel in vitro systems provide us with powerful tools to dissect the mechanism underlying the segmentation clock and the control of the timing of its oscillations.

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IBPS Seminar - Invited Speaker