In Vivo Human Somitogenesis Guides Somite Development from hPSCs

Publication date: 7 February 2017
Source:Cell Reports, Volume 18, Issue 6
Author(s): Haibin Xi, Wakana Fujiwara, Karen Gonzalez, Majib Jan, Simone Liebscher, Ben Van Handel, Katja Schenke-Layland, April D. Pyle
Somites form during embryonic development and give rise to unique cell and tissue types, such as skeletal muscles and bones and cartilage of the vertebrae. Using somitogenesis-stage human embryos, we performed transcriptomic profiling of human presomitic mesoderm as well as nascent and developed somites. In addition to conserved pathways such as WNT-β-catenin, we also identified BMP and transforming growth factor β (TGF-β) signaling as major regulators unique to human somitogenesis. This information enabled us to develop an efficient protocol to derive somite cells in vitro from human pluripotent stem cells (hPSCs). Importantly, the in-vitro-differentiating cells progressively expressed markers of the distinct developmental stages that are known to occur during in vivo somitogenesis. Furthermore, when subjected to lineage-specific differentiation conditions, the hPSC-derived somite cells were multipotent in generating somite derivatives, including skeletal myocytes, osteocytes, and chondrocytes. This work improves our understanding of human somitogenesis and may enhance our ability to treat diseases affecting somite derivatives.

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Teaser

Xi et al. transcriptomically profile developing human paraxial mesoderm and uncover pathways unique to human somitogenesis. Thus, the authors develop efficient protocols to guide human pluripotent stem cells toward somites and downstream lineages. These cells could be beneficial for basic and translational applications involving somite derivatives.


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