An In Vitro Human Segmentation Clock Model Derived from Embryonic Stem Cells

作者：Li‐Fang Chu, Daniel Mamott, Zijian Ni, Rhonda Bacher, Cathy Liu, Scott Swanson, Christina Kendziorski, Ron Stewart, James A. Thomson · 发表于：Cell Reports · 年份：2019 · DOI：10.1016/j.celrep.2019.07.090 · 被引用次数：78 · 研究领域：Pluripotent Stem Cells Research、Planarian Biology and Electrostimulation、Photoreceptor and optogenetics research

Defects in somitogenesis result in vertebral malformations at birth known as spondylocostal dysostosis (SCDO). Somites are formed with a species-specific periodicity controlled by the "segmentation clock," which comprises a group of oscillatory genes in the presomitic mesoderm. Here, we report that a segmentation clock model derived from human embryonic stem cells shows many hallmarks of the mammalian segmentation clock in vivo, including a dependence on the NOTCH and WNT signaling pathways. The gene expression oscillations are highly synchronized, displaying a periodicity specific to the human clock. Introduction of a point of mutation into HES7, a specific mutation previously associated with clinical SCDO, eliminated clock gene oscillations, successfully reproducing the defects in the segmentation clock. Thus, we provide a model for studying the previously inaccessible human segmentation clock to better understand the mechanisms contributing to congenital skeletal defects.