Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid
Abstract
Mammalian blastocysts comprise three distinct cell lineages essential for development beyond implantation: the pluripotent epiblast, which generates the future embryo, and surrounding it the extra-embryonic primitive endoderm and the trophectoderm tissues. Embryonic stem cells can reintegrate into embryogenesis but contribute primarily to epiblast lineages. Here, we show that mouse embryonic stem cells cultured under extended pluripotent conditions (EPSCs) can be partnered with trophoblast stem cells to self-organize into blastocyst-like structures with all three embryonic and extra-embryonic lineages. Morphogenetic and transcriptome profiling analyses reveal that these blastocyst-like structures show distinct embryonic-abembryonic axes and primitive endoderm differentiation and can initiate the transition from the pre- to post-implantation egg cylinder morphology in vitro.
Additional Information
© 2019 Published by Elsevier Inc. Received 10 June 2019, Revised 10 October 2019, Accepted 19 November 2019, Available online 16 December 2019. This work was supported by the European Research Council (669198), the Wellcome Trust (098287/Z/12/Z), Open Philanthropy Project, and the Curci Foundation. J.D. is supported by the BBSRC-DTP. The authors are grateful to Bill Mansfield, Lars Wittler, and Manuela Scholze-Wittler for their help with experiments to transfer embryos to the foster mothers. The authors are also thankful to Neophytos Christodoulou, Can Aztekin, Meng Zhu, and Marta Shahbazi for discussions. Data and Code Availability: The accession number for the sc-RNA sequencing data is available at Gene Expression Omnibus (GEO) dataset under accession number GSE134240. The accession number for E3.5, E4.5 and E7.5 data assembled from GSE123046 (Nowotschin et al., 2019) (data presented in Figures 2E–2G and S3). Author Contributions: Conceptualization, B.S., A.L.C., and M.Z.-G.; Methodology and Investigation, B.S. and A.L.C.; Bioinformatics Analyses, J.D. and F.H.; Experimental Assistance, M.B.; Visualization, A.L.C.; Supervision, D.M.G and M.Z.-G with the help of B.S. and A.L.C.; Writing – Original Draft & Editing, B.S., A.L.C., M.Z.-G., and D.M.G. The authors declare no competing interests.Attached Files
Accepted Version - nihms-1903730.pdf
Supplemental Material - 1-s2.0-S1534580719309451-mmc1.pdf
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Additional details
- PMCID
- PMC10291877
- Eprint ID
- 100311
- DOI
- 10.1016/j.devcel.2019.11.014
- Resolver ID
- CaltechAUTHORS:20191216-145145496
- European Research Council (ERC)
- 669198
- Wellcome Trust
- 098287/Z/12/Z
- Shurl and Kay Curci Foundation
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Created
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2019-12-16Created from EPrint's datestamp field
- Updated
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2023-06-28Created from EPrint's last_modified field