A single-cell atlas of pig gastrulation as a resource for comparative embryology

Simpson, Luke; Strange, Andrew; Klisch, Doris; Kraunsoe, Sophie; Azami, Takuya; Goszczynski, Daniel; Le Minh, Triet; Planells, Benjamin; Holmes, Nadine; Sang, Fei; Henson, Sonal; Loose, Matthew; Nichols, Jennifer; Alberio, Ramiro

Abstract

Cell-fate decisions during mammalian gastrulation are poorly understood outside of rodent embryos. The embryonic disc of pig embryos mirrors humans, making them a useful proxy for studying gastrulation. Here we present a single-cell transcriptomic atlas of pig gastrulation, revealing cell-fate emergence dynamics, as well as conserved and divergent gene programs governing early porcine, primate, and murine development. We highlight heterochronicity in extraembryonic cell-types, despite the broad conservation of cell-type-specific transcriptional programs. We apply these findings in combination with functional investigations, to outline conserved spatial, molecular, and temporal events during definitive endoderm specification. We find early FOXA2 + /TBXT- embryonic disc cells directly form definitive endoderm, contrasting later-emerging FOXA2/TBXT+ node/notochord progenitors. Unlike mesoderm, none of these progenitors undergo epithelial-to-mesenchymal transition. Endoderm/Node fate hinges on balanced WNT and hypoblast-derived NODAL, which is extinguished upon endodermal differentiation. These findings emphasise the interplay between temporal and topological signalling in fate determination during gastrulation.

Citation

Simpson, L., Strange, A., Klisch, D., Kraunsoe, S., Azami, T., Goszczynski, D., Le Minh, T., Planells, B., Holmes, N., Sang, F., Henson, S., Loose, M., Nichols, J., & Alberio, R. (2024). A single-cell atlas of pig gastrulation as a resource for comparative embryology. Nature Communications, 15(1), Article 5210. https://doi.org/10.1038/s41467-024-49407-6

• Journal Article Type: Article
• Acceptance Date: Jun 4, 2024
• Online Publication Date: Jun 18, 2024
• Publication Date: Jun 18, 2024
• Deposit Date: Jun 19, 2024
• Publicly Available Date: Jun 20, 2024
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Article Number: 5210
• DOI: https://doi.org/10.1038/s41467-024-49407-6
• Keywords: embryo, rna seq, gastrulation,
• Public URL: https://nottingham-repository.worktribe.com/output/36296303
• Publisher URL: https://www.nature.com/articles/s41467-024-49407-6
• Additional Information: Received: 21 August 2023; Accepted: 4 June 2024; First Online: 18 June 2024; : The authors declare no competing interests.