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

Luke Simpson, Andrew Strange, Doris Klisch, Sophie Kraunsoe, Takuya Azami, Daniel Goszczynski, Triet Minh, Benjamin Planells, Nadine Holmes, Fei Sang, Sonal Henson, Matthew Loose, Jennifer Nichols and Ramiro Alberio ()
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Luke Simpson: University of Nottingham, Sutton Bonington Campus
Andrew Strange: University of Nottingham, Sutton Bonington Campus
Doris Klisch: University of Nottingham, Sutton Bonington Campus
Sophie Kraunsoe: University of Nottingham, Sutton Bonington Campus
Takuya Azami: University of Edinburgh, Western General Hospital
Daniel Goszczynski: University of Nottingham, Sutton Bonington Campus
Triet Minh: University of Nottingham, Sutton Bonington Campus
Benjamin Planells: University of Nottingham, Sutton Bonington Campus
Nadine Holmes: University of Nottingham
Fei Sang: University of Nottingham
Sonal Henson: University of Nottingham
Matthew Loose: University of Nottingham
Jennifer Nichols: University of Edinburgh, Western General Hospital
Ramiro Alberio: University of Nottingham, Sutton Bonington Campus

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49407-6

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