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Reconstructing human early embryogenesis in vitro with pluripotent stem cells

View ORCID ProfileBerna Sozen, View ORCID ProfileVictoria Jorgensen, Meng Zhu, Tongtong Cui, View ORCID ProfileMagdalena Zernicka-Goetz
doi: https://doi.org/10.1101/2021.03.12.435175
Berna Sozen
1Plasticity and Self-Organization Group, Division of Biology and Biological Engineering, Caltech, Pasadena, CA 91125
3Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT 06520
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  • ORCID record for Berna Sozen
Victoria Jorgensen
1Plasticity and Self-Organization Group, Division of Biology and Biological Engineering, Caltech, Pasadena, CA 91125
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Meng Zhu
2Mammalian Development and Stem Cell Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK
4Genetics Department, Harvard Medical School, Harvard, Boston, MA 02215
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Tongtong Cui
1Plasticity and Self-Organization Group, Division of Biology and Biological Engineering, Caltech, Pasadena, CA 91125
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Magdalena Zernicka-Goetz
1Plasticity and Self-Organization Group, Division of Biology and Biological Engineering, Caltech, Pasadena, CA 91125
2Mammalian Development and Stem Cell Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK
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  • For correspondence: mz205@cam.ac.uk
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ABSTRACT

Understanding human development is of fundamental biological and clinical importance. Yet despite its significance, insights into early developmental events in humans still remain largely unknown. While recent advances show that stem cells can mimic embryogenesis1–9 to unravel hidden developmental mechanisms, a stem cell-based model of early human embryogenesis is lacking. Here, we use human extended pluripotent stem cells10to reconstitute early human development in 3-dimensions and recapitulate early embryo-like events. We first perform a systematic characterisation to reveal unique signalling requirements for building the human pre-implantation blastocyst. Further, we show that these in vitro stem cell-derived blastocyst-like structures are able to undertake spatiotemporal self-organisation to mimic peri-implantation remodelling in which a polarised rosette opens up the amniotic cavity within a developing disc. The hallmarks of human early development displayed by this stem cell-based in vitro model mimics features of embryonic day 3 to day 9/10 of natural development. Thus, this platform represents a tractable model system to contribute to the basic understanding of cellular and molecular mechanisms governing early embryonic events in humans and to provide valuable insights into the design of differentiation protocols for human stem cells in clinical applications.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 12, 2021.
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Reconstructing human early embryogenesis in vitro with pluripotent stem cells
Berna Sozen, Victoria Jorgensen, Meng Zhu, Tongtong Cui, Magdalena Zernicka-Goetz
bioRxiv 2021.03.12.435175; doi: https://doi.org/10.1101/2021.03.12.435175
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Reconstructing human early embryogenesis in vitro with pluripotent stem cells
Berna Sozen, Victoria Jorgensen, Meng Zhu, Tongtong Cui, Magdalena Zernicka-Goetz
bioRxiv 2021.03.12.435175; doi: https://doi.org/10.1101/2021.03.12.435175

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