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Bioengineered embryoids mimic post-implantation development in vitro

Mehmet U. Girgin, Nicolas Broguiere, Sylke Hoehnel, Nathalie Brandenberg, Bastien Mercier, Alfonso Martinez Arias, Matthias P. Lutolf
doi: https://doi.org/10.1101/2021.01.10.426096
Mehmet U. Girgin
1Institute of Bioengineering, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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Nicolas Broguiere
1Institute of Bioengineering, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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Sylke Hoehnel
4SUN bioscience, Biopôle, Bâtiment SE-B, Route de la Corniche 5, CH-1066 Epalinges, Switzerland
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Nathalie Brandenberg
4SUN bioscience, Biopôle, Bâtiment SE-B, Route de la Corniche 5, CH-1066 Epalinges, Switzerland
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Bastien Mercier
5Faculty of Medicine and Pharmacy, University of Grenoble Alpes, Grenoble, France
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Alfonso Martinez Arias
2Department of Genetics, University of Cambridge, Cambridge, UK
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Matthias P. Lutolf
1Institute of Bioengineering, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
3Institute of Chemical Sciences and Engineering, School of Basic Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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  • For correspondence: matthias.lutolf@epfl.ch
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Abstract

The difficulty of studying post-implantation development in mammals has sparked a flurry of activity to develop in vitro models, termed embryoids, based on self-organizing pluripotent stem cells. Previous approaches to derive embryoids either lack the physiological morphology and signaling interactions, or are not yet optimal for modeling post-gastrulation development. Here, we report a bioengineering-inspired approach aimed at addressing this gap. A high-throughput cell aggregation approach was employed to simultaneously coax mouse embryonic stem cells (ESCs) into hundreds of uniform epiblast-like (EPI) aggregates in a solid matrix-free manner. When co-cultured with mouse trophoblast stem cell (TSC) aggregates, the resulting hybrid structures initiate gastrulation-like events and undergo axial morphogenesis to yield structures, termed EpiTS embryoids, with a pronounced anterior development, including brain-like regions. We identify the presence of an epithelium in EPI aggregates as the major determinant for the axial morphogenesis and anterior development seen in EpiTS embryoids. Our results demonstrate the potential of EpiTS embryoids to study peri-gastrulation development in vitro.

Competing Interest Statement

The EPFL has filed for patent protection on the microwell array technology applied herein, and S.H., N.B. and M.P.L. are named as inventors on those patents; S.H., N.B. and M.P.L. are shareholder in SUN bioscience SA, which is commercializing those patents.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 10, 2021.
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Bioengineered embryoids mimic post-implantation development in vitro
Mehmet U. Girgin, Nicolas Broguiere, Sylke Hoehnel, Nathalie Brandenberg, Bastien Mercier, Alfonso Martinez Arias, Matthias P. Lutolf
bioRxiv 2021.01.10.426096; doi: https://doi.org/10.1101/2021.01.10.426096
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Bioengineered embryoids mimic post-implantation development in vitro
Mehmet U. Girgin, Nicolas Broguiere, Sylke Hoehnel, Nathalie Brandenberg, Bastien Mercier, Alfonso Martinez Arias, Matthias P. Lutolf
bioRxiv 2021.01.10.426096; doi: https://doi.org/10.1101/2021.01.10.426096

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