Nov 4, 2018

In vitro characterization of the human segmentation clock

BioRxiv : the Preprint Server for Biology
Margarete Diaz-CuadrosOlivier Pourquié

Abstract

The vertebral column 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. 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. Here, 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. We also demonstrate that FGF signaling controls the phase and period of the oscillator. This contrasts with classical segmentation models such as...Continue Reading

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Mentioned in this Paper

FOLH1 gene
Embryo
Biologic Segmentation
Pluripotent Stem Cells
Notch
Sequence Determinations, RNA
Receptor Down-Regulation
Intermediate Periventricular Nucleus
WNT1
Embryonic Development

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