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 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.

Automated summary

In this study, gastruloids were generated from pluripotent stem cells and single-cell genomic analysis was used to map cell states and types during their development. The researchers also identified an early spatial variability in pluripotency that determined the response to Wnt activation. A compound screen was performed on thousands of gastruloids to derive a phenotypic landscape and infer genetic interactions. This study provides important insights into the development and generation of complex patterns in gastruloids.