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?:abstract
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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 non-diseased lung 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
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