Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro
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Harrison, S., Sozen, B., Christodoulou, N., Kyprianou, C., & Zernicka-Goetz, M. (2017). Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science, 356 (6334. eaal1810)https://doi.org/10.1126/science.aal1810
Mammalian embryogenesis requires intricate interactions between embryonic and extraembryonic tissues to orchestrate and coordinate morphogenesis with changes in developmental potential. Here, we combined mouse embryonic stem cells (ESCs) and extraembryonic trophoblast stem cells (TSCs) in a three-dimensional scaffold to generate structures whose morphogenesis is markedly similar to that of natural embryos. By using genetically modified stem cells and specific inhibitors, we show that embryogenesis of ESC- and TSC-derived embryos—ETS-embryos—depends on cross-talk involving Nodal signaling. When ETS-embryos develop, they spontaneously initiate expression of mesoderm and primordial germ cell markers asymmetrically on the embryonic and extraembryonic border, in response to Wnt and BMP signaling. Our study demonstrates the ability of distinct stem cell types to self-assemble in vitro to generate embryos whose morphogenesis, architecture, and constituent cell types resemble those of natural embryos.
We are grateful to the Wellcome Trust and ERC for supporting this work. S.E.H. and C.K. are both supported by Biotechnology and Biological Sciences Research Council doctoral training partnership studentships. B.S. is supported by the International Research Fellowship Program 2214/A from Scientific and Technological Research Council of Turkey, and M.Z.-G. by the Wellcome Trust. S.E.H. served as an intern in the Cambridge, UK, office of Science/AAAS.
External DOI: https://doi.org/10.1126/science.aal1810
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264047