Primate gastrulation and early organogenesis at single-cell resolution

Nature. 2022 Dec;612(7941):732-738. doi: 10.1038/s41586-022-05526-y. Epub 2022 Dec 14.

Abstract

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryoid Bodies
  • Gastrulation* / genetics
  • Gene Expression Profiling
  • Hippo Signaling Pathway
  • Humans
  • Macaca fascicularis* / embryology
  • Macaca fascicularis* / genetics
  • Mesoderm / cytology
  • Mesoderm / embryology
  • Mice
  • Neural Crest / cytology
  • Neural Crest / embryology
  • Neural Tube / cytology
  • Neural Tube / embryology
  • Organogenesis* / genetics
  • Primitive Streak / cytology
  • Primitive Streak / embryology
  • Single-Cell Analysis*
  • Stem Cells