Respiratory failure associated with COVID-19 has placed focus on the lung. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched single-nucleus transcriptomes of 46,500 nuclei in healthy lung donors of ~30 weeks gestation, ~3 years and ~30 years. We mapped 398,395 candidate cis-regulatory elements (cCREs) in lung cell types and linked distal cCREs to putative target genes and leveraged this dataset to investigate loci associated with COVID-19. At the SARS-CoV-2 host entry gene TMPRSS2, we identified distal cCREs with age-increased activity in alveolar type 2 cells which had immune regulatory signatures and harbored variants associated with respiratory traits. At the novel 3p21.31 COVID-19 risk locus, a candidate variant overlapped a distal cCRE linked to SLC6A20, a gene expressed in alveolar cells which has known functional association with ACE2. Our findings provide insight into the gene regulatory logic of lung cell types including likely drivers of the increased expression of SARS-CoV-2 host genes in adults, and establish a resource (lungepigenome.org) for interpreting lung disease risk.

Link to the paper : https://elifesciences.org/articles/62522
Link to all the datasets : GEO: GSE161383