%0 Journal Article
%T A single-cell atlas of pig gastrulation as a resource for comparative embryology.
%A Simpson L
%A Strange A
%A Klisch D
%A Kraunsoe S
%A Azami T
%A Goszczynski D
%A Le Minh T
%A Planells B
%A Holmes N
%A Sang F
%A Henson S
%A Loose M
%A Nichols J
%A Alberio R
%J Nat Commun
%V 15
%N 1
%D 2024 Jun 18
%M 38890321
%F 17.694
%R 10.1038/s41467-024-49407-6
%X 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.