Respiratory failure associated with COVID-19 has placed focus on the lungs. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched single-nucleus transcriptomes of 46,500 nuclei in non-diseased lungs from donors of ~30 weeks gestation,~3 years and ~30 years. We mapped candidate cis -regulatory elements (cCREs) and linked them to putative target genes. We identified distal cCREs with age-increased activity linked to SARS-CoV-2 host entry gene TMPRSS2 in alveolar type 2 cells, which had immune regulatory signatures and harbored variants associated with respiratory traits. At the 3p21.31 COVID-19 risk locus, a candidate variant overlapped a distal cCRE linked to SLC6A20 , a gene expressed in alveolar cells and with known functional association with the SARS-CoV-2 receptor ACE2. Our findings provide insight into regulatory logic underlying genes implicated in COVID-19 in individual lung cell types across age. More broadly, these datasets will facilitate interpretation of risk loci for lung diseases.
【저자키워드】 COVID-19, Human, lung, Gene regulation, single cell RNA/ATAC-seq, cis-regulatory elements, human sequence variants, 【초록키워드】 Transcriptome, SARS-CoV-2, TMPRSS2, Respiratory failure, variant, risk, immune, SARS-CoV-2 receptor, Regulatory, cells, Lungs, Lung diseases, Interpretation, age, dataset, donors, respiratory, Donor, association, Target genes, cell types, transcriptomes, focus, locus, profile, traits, receptor ACE2, chromatin, element, alveolar cells, alveolar, putative target genes, risk loci, SLC6A20, Host, lung cell, nuclei, facilitate, functional, expressed, alveolar cell, mapped, implicated, distal, overlapped, the SARS-CoV-2, with COVID-19, 【제목키워드】 SARS-CoV2, human lung, reveal, host gene,