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Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro

Harrison, Sarah Ellys and Sozen, Berna and Christodoulou, Neophytos and Kyprianou, Christos and Zernicka-Goetz, Magdalena (2017) Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science, 356 (6334). Art. No. eaal1810. ISSN 0036-8075. https://resolver.caltech.edu/CaltechAUTHORS:20190405-170314754

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1126/science.aal1810DOIArticle
https://doi.org/10.1126/science.aan1495Featured InScience : Perspective
http://www.sciencemag.org/content/356/6334/eaal1810/suppl/DC1PublisherSupporting Information
ORCID:
AuthorORCID
Harrison, Sarah Ellys0000-0002-1571-2399
Sozen, Berna0000-0001-5834-5819
Christodoulou, Neophytos0000-0003-4338-5847
Kyprianou, Christos0000-0001-8516-9195
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2017 American Association for the Advancement of Science. 9 October 2016; accepted 17 February 2017. Published online 2 March 2017 We are grateful to D. Glover, M. Shahbazi, S. Vuoristo, and F. Antonica for helpful feedback on the manuscript; A. Hupalowska for drawing models (Figs. 1A, 2I, and 8) and G. Recher for 3D rendering (Fig. 1, B and D); the creators of the “Bioemergences” platform for providing image analysis tools; and V. Kuskoff, A. Surani, and B. Herrmann for providing T:GFP ESCs and Stella:GFP ESCs. 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. M.Z.-G. and S.E.H. are inventors on a patent application (1615343.9) submitted by Cell Guidance Systems, in which the University of Cambridge and the Wellcome Trust are beneficiaries, that covers the method and medium composition used to generate “stem cell–derived embryos.” S.E.H. and B.S. carried out experiments and data analysis on ETS-embryos. N.C. and C.K. carried out experiments on natural embryos. M.Z.-G. conceived and supervised the study and wrote the paper with the help of S.E.H. and B.S.
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
European Research Council (ERC)UNSPECIFIED
Biotechnology and Biological Sciences Research Council (BBSRC)UNSPECIFIED
Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK)2214/A
Issue or Number:6334
Record Number:CaltechAUTHORS:20190405-170314754
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190405-170314754
Official Citation:Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro BY SARAH ELLYS HARRISON, BERNA SOZEN, NEOPHYTOS CHRISTODOULOU, CHRISTOS KYPRIANOU, MAGDALENA ZERNICKA-GOETZ Science 14 Apr 2017: Vol. 356, Issue 6334, eaal1810 DOI: 10.1126/science.aal1810
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94534
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 18:40
Last Modified:03 Oct 2019 21:04

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