Author: Wang, Allen; Chiou, Joshua; Poirion, Olivier B; Buchanan, Justin; Valdez, Michael J; Verheyden, Jamie M; Hou, Xiaomeng; Kudtarkar, Parul; Narendra, Sharvari; Newsome, Jacklyn M; Guo, Minzhe; Faddah, Dina A; Zhang, Kai; Young, Randee E; Barr, Justinn; Sajti, Eniko; Misra, Ravi; Huyck, Heidie; Rogers, Lisa; Poole, Cory; Whitsett, Jeffery A; Pryhuber, Gloria; Xu, Yan; Gaulton, Kyle J; Preissl, Sebastian; Sun, Xin
Title: Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes Cord-id: hco6zfoj Document date: 2020_11_9
ID: hco6zfoj
Snippet: 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
Document: 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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