Mouse-embryo model derived exclusively from embryonic stem cells undergo neurulation and heart development
Abstract
Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extra-embryonic lineages of the post-implantation embryo by transcription factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation, and formation of the anterior-posterior axis, brain, a beating heart structure, and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages, but also showed when and where the model diverges from the natural program. Our findings demonstrate an extra-ordinary plasticity of ESCs to self-organize and generate a whole embryo-like structure.
Additional Information
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. The authors would like to thank David Glover and Ron Hadas for helpful comments, Yoav Mayshar for his assistance with sample collection for MARS-seq, Netta Reines for technical support with scRNA-seq processing, and the flow cytometry facility from the School of the Biological Sciences, University of Cambridge for their assistance in this work. The grants to M.Z.-G that supported this work are: NIH Pioneer Award (DP1 HD104575-01), European Research Council (669198), the Wellcome Trust (207415/Z/17/Z), Open Philanthropy/Silicon Valley Community Foundation and Weston Havens Foundation. The grants to YS that supported this work are: European Research Council (ERC_StG 852865) and Helen and Martin Kimmel Stem Cell Institute. K.Y.C.L. is supported by the Croucher Foundation and the Cambridge Trust. C.W.G. is supported by a Leverhulm Early Career Research Fellowship. Research in the M.Z.-G and Y.S. labs is supported by the Schwartz/Reisman Collaborative Science Program. Author contributions. Conceptualisation: G.A., Y.S., M.Z.-G.; Data curation: H.R.; Formal Analysis: K.Y.C.L., H.R.; Funding acquisition: Y.S., M.Z.-G.; Investigation: K.Y.C.L., C.W.G.; Methodology: K.Y.C.L., G.A.; Software: H.R.; Visualisation: K.Y.C.L., H.R.; Supervision: Y.S., M.Z.-G.; Writing: K.Y.C.L., H.R., Y.S., and M.Z.-G. The authors have declared no competing interest.Attached Files
Submitted - 2022.08.01.502371v1.full.pdf
Supplemental Material - media-1.mp4
Supplemental Material - media-2.mp4
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Additional details
- Eprint ID
- 116063
- Resolver ID
- CaltechAUTHORS:20220803-224511000
- DP1 HD104575-01
- NIH
- 669198
- European Research Council (ERC)
- 207415/Z/17/Z
- Wellcome Trust
- Open Philanthropy
- Silicon Valley Community Foundation
- Weston Havens Foundation
- 852865
- European Research Council (ERC)
- Helen and Martin Kimmel Stem Cell Institute
- Croucher Foundation
- Cambridge Trust
- Leverhulme Trust
- Schwartz/Reisman Collaborative Science Program
- Created
-
2022-08-03Created from EPrint's datestamp field
- Updated
-
2022-08-03Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering