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

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.

Datasets

1. Single-cell multiomic profiling of human lungs across age groups
Metadata
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celltype
lineage
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D0468894 cells
D1506271 cells
D0885903 cells
D1395217 cells
D0324970 cells
D0624852 cells
D2314680 cells
D1223935 cells
D1751778 cells
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Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes

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Source data

https://cellxgene.cziscience.com/collections/625f6bf4-2f33-4942-962e-35243d284837

Alias names

LungMAP, phs001961, GSE161382, PMID33164753, PMC7688309

Cite this study

Wang, A., Chiou, J., Poirion, O.B., Buchanan, J., Valdez, M.J., Verheyden, J.M., Hou, X., Kudtarkar, P., Narendra, S., Newsome, J.M. and Guo, M., 2020. Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes. Elife, 9, p.e62522. https://doi.org/10.7554/eLife.62522