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- Title
Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes.
- Authors
Wang, Allen; Chiou, Joshua; Poirion, Olivier B.; Buchanan, Justin; Valdez, Michael J.; Verheyden, Jamie M.; Xiaomeng Hou; Kudtarkar, Parul; Narendra, Sharvari; Newsome, Jacklyn M.; Guo, Minzhe; Faddah, Dina A.; Kai Zhang; Young, Randee E.; Barr, Justinn; Sajti, Eniko; Misra, Ravi; Huyck, Heidie; Rogers, Lisa; Poole, Cory
- Abstract
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.
- Subjects
SARS-CoV-2; COVID-19; LUNG diseases; GENES; ANGIOTENSIN converting enzyme; LUNGS
- Publication
eLife, 2020, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.62522