Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures.
Authors
Amadei, Gianluca
Cox, Andy
Wang, Ran
Czukiewska, Sylwia
Chappell, Lia
Voet, Thierry
Michel, Geert
Jing, Naihe
Publication Date
2018-08Journal Title
Nat Cell Biol
ISSN
1465-7392
Publisher
Springer Science and Business Media LLC
Volume
20
Issue
8
Pages
979-989
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Sozen Kaya, B., Amadei, G., Cox, A., Wang, R., Na, E., Czukiewska, S., Chappell, L., et al. (2018). Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures.. Nat Cell Biol, 20 (8), 979-989. https://doi.org/10.1038/s41556-018-0147-7
Abstract
Embryonic stem cells can be incorporated into the developing embryo and its germ line, but, when cultured alone, their ability to generate embryonic structures is restricted. They can interact with trophoblast stem cells to generate structures that break symmetry and specify mesoderm, but their development is limited as the epithelial-mesenchymal transition of gastrulation cannot occur. Here, we describe a system that allows assembly of mouse embryonic, trophoblast and extra-embryonic endoderm stem cells into structures that acquire the embryo's architecture with all distinct embryonic and extra-embryonic compartments. Strikingly, such embryo-like structures develop to undertake the epithelial-mesenchymal transition, leading to mesoderm and then definitive endoderm specification. Spatial transcriptomic analyses demonstrate that these morphological transformations are underpinned by gene expression patterns characteristic of gastrulating embryos. This demonstrates the remarkable ability of three stem cell types to self-assemble in vitro into gastrulating embryo-like structures undertaking spatio-temporal events of the gastrulating mammalian embryo.
Keywords
Cell Line, Trophoblasts, Endoderm, Animals, Mice, Coculture Techniques, Cell Communication, Cell Differentiation, Cell Movement, Gene Expression Regulation, Developmental, Cell Lineage, Gestational Age, Phenotype, Embryo, Mammalian, Gastrulation, Epithelial-Mesenchymal Transition, Transcriptome, Mouse Embryonic Stem Cells
Sponsorship
European Research Council (669198)
Wellcome Trust (098287/Z/12/Z).
Funder references
Wellcome Trust (098287/Z/12/Z)
European Research Council (669198)
Identifiers
External DOI: https://doi.org/10.1038/s41556-018-0147-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/294716
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