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

Nat Commun. 2024 Jun 18;15(1):5210. doi: 10.1038/s41467-024-49407-6.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Embryo, Mammalian* / cytology
  • Embryo, Mammalian* / metabolism
  • Endoderm* / cytology
  • Endoderm* / embryology
  • Endoderm* / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Gastrulation*
  • Gene Expression Regulation, Developmental*
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocyte Nuclear Factor 3-beta / metabolism
  • Mesoderm / cytology
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Mice
  • Single-Cell Analysis*
  • Swine
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcriptome

Substances

  • Hepatocyte Nuclear Factor 3-beta
  • T-Box Domain Proteins