Abstract
AbstractEarly mammalian gastrulation’s 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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