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

Simpson, L.; Strange, A.; Klisch, D.; Kraunsoe, S.; Azami, T.; Goszczynski, D.; Le, T.; Planells, B.; Holmes, N.; Sang, F.; Henson, S.; Loose, M. W.; Nichols, J.; Alberio, R.

doi:10.1101/2023.08.31.555712

bioRxiv · 10.1101/2023.08.31.555712

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

Simpson, L.·Strange, A.·Klisch, D.·Kraunsoe, S.·Azami, T.·Goszczynski, D.·Le, T.·Planells, B.·Holmes, N.·Sang, F.·Henson, S.·Loose, M. W.·Nichols, J.·Alberio, R.

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Abstract

Early mammalian gastrulations cell-fate decisions are poorly understood due to difficulties obtaining non-rodent embryos. The bilaminar 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-type development, 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 (DE). We find early FOXA2+/TBXT-embryonic disc cells directly from DE, contrasting later-emerging FOXA2/TBXT+ node/notochord progenitors. Unlike mesoderm, none of these progenitors undergo epithelial-to-mesenchymal transition. DE/Node fate hinges on balanced WNT and hypoblast-derived NODAL, which is extinguished upon DE differentiation. These findings emphasise the interplay between temporal and topological signalling in early fate decisions during gastrulation.

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Simpson, L., Strange, A., Klisch, D., Kraunsoe, S., Azami, T., Goszczynski, D., Le, T., Planells, B., Holmes, N., Sang, F., Henson, S., Loose, M. W., Nichols, J., Alberio, R.. 2023-09-02. A single-cell atlas of pig gastrulation as a resource for comparative embryology. https://doi.org/10.1101/2023.08.31.555712

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