Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes

Allen Wang, Joshua Chiou, Olivier B Poirion, Justin Buchanan, Michael J Valdez, Jamie M Verheyden, Xiaomeng Hou, Parul Kudtarkar, Sharvari Narendra, Jacklyn M Newsome, Minzhe Guo, Dina A Faddah, Kai Zhang, Randee E Young, Justinn Barr, Eniko Sajti, Ravi Misra, Heidie Huyck, Lisa Rogers, Cory Poole, Jeffery A Whitsett, Gloria Pryhuber, Yan Xu, Kyle J Gaulton, Sebastian Preissl, Xin Sun, NHLBI LungMap Consortium.
eLife. 2020-11-09;9:e62522.
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.

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sci-ATAC-seq data of human lung samples: dbGaP: phs001961