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Multimodal characterization of murine gastruloid development

Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development and compare them with the in vivo embryo. We...

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Detalles Bibliográficos
Autores principales: Suppinger, Simon, Zinner, Marietta, Aizarani, Nadim, Lukonin, Ilya, Ortiz, Raphael, Azzi, Chiara, Stadler, Michael B., Vianello, Stefano, Palla, Giovanni, Kohler, Hubertus, Mayran, Alexandre, Lutolf, Matthias P., Liberali, Prisca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241222/
https://www.ncbi.nlm.nih.gov/pubmed/37209681
http://dx.doi.org/10.1016/j.stem.2023.04.018
Descripción
Sumario:Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development and compare them with the in vivo embryo. We developed a high-throughput handling and imaging pipeline to spatially monitor symmetry breaking during gastruloid development and report an early spatial variability in pluripotency determining a binary response to Wnt activation. Although cells in the gastruloid-core revert to pluripotency, peripheral cells become primitive streak-like. These two populations subsequently break radial symmetry and initiate axial elongation. By performing a compound screen, perturbing thousands of gastruloids, we derive a phenotypic landscape and infer networks of genetic interactions. Finally, using a dual Wnt modulation, we improve the formation of anterior structures in the existing gastruloid model. This work provides a resource to understand how gastruloids develop and generate complex patterns in vitro.