Bioengineered embryoids mimic post-implantation development in vitro

Mehmet U. Girgin, Nicolas Broguiere, Sylke Hoehnel, Nathalie Brandenberg, Bastien Mercier, Alfonso Martinez Arias and Matthias P. Lutolf ()
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Mehmet U. Girgin: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)
Nicolas Broguiere: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)
Sylke Hoehnel: SUN bioscience, EPFL Innovation Park
Nathalie Brandenberg: SUN bioscience, EPFL Innovation Park
Bastien Mercier: University of Grenoble Alpes
Alfonso Martinez Arias: University of Cambridge
Matthias P. Lutolf: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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 unconducive to model post-gastrulation development. Here, we report a bioengineering-inspired approach aimed at addressing this gap. We employ a high-throughput cell aggregation approach to simultaneously coax mouse embryonic stem cells into hundreds of uniform epiblast-like aggregates in a solid matrix-free manner. When co-cultured with mouse trophoblast stem cell 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.

Date: 2021
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DOI: 10.1038/s41467-021-25237-8

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