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Suppinger, S.* ; Zinner, M.* ; Aizarani, N.* ; Lukonin, I.* ; Ortiz, R.* ; Azzi, C.* ; Stadler, M.B.* ; Vianello, S.* ; Palla, G. ; Kohler, H.* ; Mayran, A.* ; Lutolf, M.P.* ; Liberali, P.*

Multimodal characterization of murine gastruloid development.

Cell Stem Cell 30, 867-884.e11 (2023)
Publ. Version/Full Text DOI PMC
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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
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Journal Cell Stem Cell
Quellenangaben Volume: 30, Issue: 6, Pages: 867-884.e11 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-001
Grants Swiss National Science Foundation (SNF)
European Research Council (ERC)
Human Frontier Science Program
SNSF Sinergia grant
European Research Council under the European Union
DOI 10.1016/j.stem.2023.04.018
WOS ID 001013216300001
Scopus ID 85160968122
PubMed ID 37209681
Erfassungsdatum 2023-10-06
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