A single-cell RNA expression map of coronavirus receptors and associated factors in developing human embryos

TL;DR

This study maps the expression of coronavirus receptors and related factors in developing human embryos using single-cell RNA sequencing, suggesting potential susceptibility to SARS-CoV-2 entry and replication during early development.

Contribution

It provides the first comprehensive single-cell RNA-seq analysis of coronavirus receptor expression in human embryos, revealing possible mechanisms of viral entry and replication in early development stages.

Findings

ACE2 and other receptors are expressed from zygote to blastocyst stages.

Co-expression of ACE2 and TMPRSS2 occurs in epiblast and trophectoderm cells.

Genes involved in viral replication and endocytosis are also expressed in embryonic cells.

Abstract

To predict if developing human embryos are permissive to coronaviruses, we analyzed publicly available single cell RNA-seq datasets of zygotes, 4-cell, 8-cell, morula, inner cell mass, epiblast, primitive endoderm and trophectoderm for the coronavirus receptors (ACE2, BSG, DPP4 and ANPEP), the Spike protein cleavage enzymes (TMPRSS2, CTSL). We also analyzed the presence of host genes involved in viral replication, the endosomal sorting complexes required for transport (ESCRT) and SARS-Cov-2 interactions. The results reveal that ACE2, BSG, DPP4 and ANPEP are expressed in the cells of the zygote, to blastocyst including the trophectodermal lineage. ACE2, TMPRSS, BSG and CTSL are co-transcribed in a proportion of epiblast cells and most cells of the trophectoderm. The embryonic and trophectodermal cells also express genes for proteins ESCRT, viral replication and those that interact with SARS-CoV-2. We identified 1985 genes in epiblast and 1452 genes in the trophectoderm that are enriched in the ACE2 and TMPRSS2 co-expressing cells; 216 genes of these are common in both the cell types. These genes are associated with lipid metabolism, lysosome, peroxisome and oxidative phosphorylation pathways. Together our results suggest that developing human embryos could be permissive to coronavirus entry by both canonical and non-canonical mechanisms and they also express the genes for proteins involved in viral endocytosis and replication. This knowledge will be useful for evidence-based patient management for IVF during the COVID-19 pandemic.