Bioengineered embryoids mimic post-implantation development in vitro

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 interacti...

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Detalhes bibliográficos
Autores: Girgin, Mehmet U., Broguiere, Nicolas, Hoehnel, Sylke, Brandenberg, Nathalie, Mercier, Bastien, Martinez Arias, Alfonso, Lutolf, Matthias P.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/52727
Acesso em linha:http://hdl.handle.net/10230/52727
http://dx.doi.org/10.1038/s41467-021-25237-8
Access Level:Acceso aberto
Palavra-chave:Biological models
Biomedical engineering
Embryology
Embryonic stem cells
Stem-cell differentiation
Descrição
Resumo: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.