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Multimodal characterization of murine gastruloid development.
Cell Stem Cell 30, 867-884.e11 (2023)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cell States ; Embryoids ; Gastruloids ; Imaging ; Pluripotency ; Screening ; Symmetry Breaking; Symmetry-breaking; Self-organization; Mouse; Pluripotency; Specification; Expression; Nanog; Cells; Gene; Sox2
ISSN (print) / ISBN
1934-5909
e-ISSN
1875-9777
Journal
Cell Stem Cell
Quellenangaben
Volume: 30,
Issue: 6,
Pages: 867-884.e11
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Grants
Swiss National Science Foundation (SNF)
European Research Council (ERC)
Human Frontier Science Program
SNSF Sinergia grant
European Research Council under the European Union
European Research Council (ERC)
Human Frontier Science Program
SNSF Sinergia grant
European Research Council under the European Union