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Reconstructing human early embryogenesis in vitro with pluripotent stem cells

Sozen, Berna and Jorgensen, Victoria and Zhu, Meng and Cui, Tongtong and Zernicka-Goetz, Magdalena (2021) Reconstructing human early embryogenesis in vitro with pluripotent stem cells. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210317-080317393

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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 embryogenesis to unravel hidden developmental mechanisms, a stem cell-based model of early human embryogenesis is lacking. Here, we use human extended pluripotent stem cells to 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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.03.12.435175DOIDiscussion Paper
ORCID:
AuthorORCID
Sozen, Berna0000-0001-5834-5819
Jorgensen, Victoria0000-0002-4205-6198
Zhu, Meng0000-0001-6157-8840
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This version posted March 12, 2021. We are grateful to David Glover and Andy Cox for their helpful discussion and comments on the manuscript. We are grateful to Rachel S. Mandelbaum, Richard J. Paulson, Ali Ahmady and USC Fertility for their help and support to obtain images shown in Figure 1E; Angel Martin, Maria J. de los Santos and IVIRMA Valencia for images shown in Figure 2E. Human TSCs were kindly provided by Hiroaki Okae and Takahiro Arima (Tohoku University Graduate School of Medicine, Japan). The Zernicka-Goetz Lab is funded by the Welcome Trust (098287/Z/12/Z), the NIH Pioneer Award Fund (DP1 HD104575-01), Open Philanthropy/Silicon Valley Community Foundation, Weston Havens Foundation and Shurl and Kay Curci Foundation to M.ZG. B.S. is now funded by Yale School of Medicine start-up award. Author Contributions: B.S. designed and performed experiments and analysed the data with the help of V.J. M.Z. provided data on human embryos. T.C performed conversion protocol for hPSCs to hTESCs. B.S., V.J. and M.ZG wrote the manuscript. B.S and M.ZG. conceived and supervised the project. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
Wellcome Trust098287/Z/12/Z
NIHDP1 HD104575-01
Open PhilanthropyUNSPECIFIED
Silicon Valley Community FoundationUNSPECIFIED
Weston Havens FoundationUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Yale UniversityUNSPECIFIED
DOI:10.1101/2021.03.12.435175
Record Number:CaltechAUTHORS:20210317-080317393
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210317-080317393
Official Citation: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
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108455
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Mar 2021 20:57
Last Modified:19 Apr 2021 22:01

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