- Main
Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes.
- Author(s): 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
- NHLBI LungMap Consortium
- et al.
Published Web Location
https://doi.org/10.7554/elife.62522Abstract
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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