Bioengineered embryoids mimic post-implantation development in vitro

• Published in: Nature communications Vol. 12; no. 1; p. 5140
• Main Authors: Girgin, Mehmet U., Broguiere, Nicolas, Hoehnel, Sylke, Brandenberg, Nathalie, Mercier, Bastien, Arias, Alfonso Martinez, Lutolf, Matthias P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/100; 13/107; 631/136/1455; 631/1647/767; 631/532/1360; 631/532/2117; 639/166/985; Aggregates; Animals; Bioengineering; Biomimetics; Cell aggregation; Cell Differentiation; Cell Proliferation; Cytology; Embryo cells; Embryo Implantation; Embryo, Mammalian - cytology; Embryo, Mammalian - embryology; Embryogenesis; Embryoid Bodies - cytology; Embryonic Development; Epithelium; Female; Gastrulation; Germ Layers - cytology; Humanities and Social Sciences; Humans; Hybrid structures; Implantation; Mice - embryology; Morphogenesis; Morphology; Mouse Embryonic Stem Cells - cytology; multidisciplinary; Physiology; Pluripotency; Science; Science (multidisciplinary); Signaling; Stem cell transplantation; Stem cells; Trophoblasts - cytology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25237-8

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. Previous approaches to derive embryoids either lack physiological morphology and signaling interactions, or are unconducive to model post-gastrulation development. Here the authors use a high-throughput approach to induce mouse embryonic stem cells into epiblast-like aggregates, which are then co-cultured with mouse trophoblast stem cell aggregates, to yield embryoids with axial morphogenesis and anterior development.