Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis

Abstract

High-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are largely inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development. For further insight on pluripotent states and lineage delineation, we analysed pig embryos at single cell resolution. Here we show progressive segregation of inner cell mass and trophectoderm in early blastocysts, and of epiblast and hypoblast in late blastocysts. We show that following an emergent short naive pluripotent signature in early embryos, there is a protracted appearance of a primed signature in advanced embryonic stages. Dosage compensation with respect to the X-chromosome in females is attained via X-inactivation in late epiblasts. Detailed human-pig comparison is a basis towards comprehending early human development and a foundation for further studies of human pluripotent stem cell differentiation in pig interspecies chimeras.

Abstract

Lineage segregation from conception to gastrulation has been mapped at the single cell level in mouse, human and monkey. Here, the authors provide a comprehensive analysis of porcine preimplantation development using single cell RNA-seq; mapping metabolic changes, X chromosome inactivation and signalling pathways.