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Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures

Sozen, Berna and Amadei, Gianluca and Cox, Andy and Wang, Ran and Na, Ellen and Czukiewska, Sylwia and Chappell, Lia and Voet, Thierry and Michel, Geert and Jing, Naihe and Glover, David M. and Zernicka-Goetz, Magdalena (2018) Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures. Nature Cell Biology, 20 (8). pp. 979-989. ISSN 1465-7392. https://resolver.caltech.edu/CaltechAUTHORS:20190408-111046182

[img] Image (JPEG) (Supplementary Figure 1: Self-assembly of ESCs, TSCs, and XEN cells into ETX embryos) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 2: Posterior patterning in ETX embryos) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 3: Basement membrane and pro-amniotic cavity formation in ETX embryos) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 4: Anterior-posterior patterning in ETX embryos) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 5: EMT events in ETX embryos) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 6: Specification of axial mesoderm in ETX embryos) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 7: Transcriptional profiling of ETX embryos reveals global similarity of anterior-posterior patterning to natural embryos) - Supplemental Material
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[img] PDF (Supplementary Figures 1–7, Supplementary Table and Supplementary Video legends) - Supplemental Material
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[img] PDF (Reporting Summary) - Supplemental Material
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[img] MS Excel (Supplementary Table 1. Antibodies used in this study) - Supplemental Material
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[img] MS Excel (Supplementary Table 2. qPCR primers used in this study) - Supplemental Material
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[img] MS Excel (Supplementary Table 3. Statistic source data) - Supplemental Material
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[img] Video (QuickTime) (Supplementary Video 1. Time-lapse recording of an ETX embryo from day 3.5 to 5.0 in culture) - Supplemental Material
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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41556-018-0147-7DOIArticle
https://rdcu.be/bvp3iPublisherFree ReadCube access -- Article
https://doi.org/10.1038/s41556-018-0187-zDOICorrection
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ORCID:
AuthorORCID
Sozen, Berna0000-0001-5834-5819
Wang, Ran0000-0003-4956-5742
Na, Ellen0000-0003-1395-9707
Jing, Naihe0000-0003-1509-6378
Glover, David M.0000-0003-0956-0103
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2018 Springer Nature Publishing AG. Received: 18 April 2018; Accepted: 20 June 2018; Published online: 23 July 2018. The authors thank colleagues in the M.Z.G. laboratory for insightful comments. The M.Z.G. laboratory is supported by grants from the European Research Council (669198) and the Wellcome Trust (098287/Z/12/Z). B.S. is also supported by Akdeniz University, Turkey. T.V. and L.C. are funded by Wellcome. T.V. is also funded by the University of Leuven, Belgium (PFV/10/016). The authors thank A. Weberling, M. Mole, N. Christodoulou, C. Kyprianou and J. Guo for their help, A. Hupalowska for inspiration for a model in Fig. 7f, and L. Wittler, I. Urban, A. Landsberger, C. Schick and H. Schlenger for technical support. These authors contributed equally:Berna Sozen, Gianluca Amadei. Author Contributions: B.S., G.A. and A.C. with the help of S.C. carried out experiments and data analysis. R.W. and N.J. analysed the sequencing data. E.N. and G.M. contributed to stem cell derivation and the experimental design. L.C. prepared cDNA libraries. T.V. supervised the cDNA library preparation. D.M.G. co-supervised parts of the study. M.Z.G. conceived and supervised the study, and wrote the paper with the help of B.S., G.A. and D.M.G. Data availability: RNA–seq data that support the findings of this study have been deposited in the Gene Expression Omnibus (GEO) under accession code GSE110105. LCM sequencing data are available under accession no. GSE65924. Source data for RT–qPCR experiments (Fig. 4c and Supplementary Fig. 2i) and quantifications of the immunofluorescence data (Figs. 1f, 2a–c and 3e and Supplementary Figs. 2d-f-g, 4c and 5d,h) and the DEG list (Fig. 7b) are provided in Supplementary Table 3. All other data supporting the findings of this study are available from the corresponding author on reasonable request. The authors declare no competing interests. Change history: 08 August 2018In the version of this Technical Report originally published, the competing interests statement was missing. The authors declare no competing interests; this statement has now been added in all online versions of the Report.
Errata:Correction to: Nature Cell Biology https://doi.org/10.1038/s41556-018-0147-7, published online 23 July 2018. In the version of this Technical Report originally published, the competing interests statement was missing. The authors declare no competing interests; this statement has now been added in all online versions of the Report.
Funders:
Funding AgencyGrant Number
European Research Council (ERC)669198
Wellcome Trust098287/Z/12/Z
Akdeniz UniversityUNSPECIFIED
Katholieke Universiteit LeuvenPFV/10/016
Issue or Number:8
Record Number:CaltechAUTHORS:20190408-111046182
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190408-111046182
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94566
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 15:14
Last Modified:09 Mar 2020 13:19

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