Abstract

Implantation of the mouse blastocyst initiates a sequence of remodelling and differentiation events that lead to the formation of the post-implantation egg cylinder. During this process, the primitive endoderm differentiates into the visceral endoderm. To elucidate extraembryonic endoderm lineage progression in peri-implantation embryos, we generated a single-cell sequencing dataset of E5.0 embryos. Our analysis shows that primitive to visceral endoderm transition includes an intermediate state which exhibits distinct signalling activities, including upregulation of Bmp signalling and transient downregulation of basement membrane component Lama1. Assessment of Hnf1b-/ embryos, which degenerate upon implantation, reveals a previously unknown interaction between epiblast and visceral endoderm required for epiblast post-implantation survival. Single-cell profiling of the Hnf1b/- E5.0 visceral endoderm demonstrates developmental delay, misexpression of the pluripotency marker Pou5f1 and consistent loss of nutrient transport pathways. These results suggest that upregulation of nutrient transport pathways during the primitive to visceral endoderm differentiation is essential for successful post-implantation development.