Single cell multiomic profiling of human lung reveals cell type-specific and age-dynamic control of SARS-CoV2 host genes
- University of California, San Diego, United States
- Cincinnati Children's Hospital Medical Center/University of Cincinnati College of Medicine, United States
- Vertex Pharmaceuticals, United States
- Ludwig Institute for Cancer Research, United States
- University of Rochester Medical Center, United States
- Cincinnati Children's Hospital Medical Center, United States
- CCHMC/University of Cincinnati, United States
Abstract
Respiratory failure associated with COVID-19 has placed focus on the lung. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched single-nucleus transcriptomes of 46,500 nuclei in non-diseased lung 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.
Data availability
Processed data including the full list of peaks are available for download and can be explored using the web portal www.lungepigenome.org. Raw sequencing files has been submitted to LungMap Data Collecting Core and will be submitted to dbGAP.Source data for Figure 1 - figure supplement 1 is available as Supplementary Table 2; Source data for Figure 3B and Figure 3 - figure supplement 1A is available as Supplementary Table 3. Source data for Figure 3E is available as Supplementary Table 4. Source data for Figure 3F is available as Supplementary Table 5. Source data for Figure 3G is available as Supplementary Table 6.Source data for Figure 4A is available as Supplementary Table 7.
Article and author information
Author details
Funding
National Heart, Lung, and Blood Institute (1U01HL148867)
- Allen Wang
- Jamie M Verheyden
- Sebastian Preissl
- Xin Sun
National Heart, Lung, and Blood Institute (U01HL122700)
- Gloria Pryhuber
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Edward E Morrisey, University of Pennsylvania, United States
Version history
- Received: August 27, 2020
- Accepted: November 8, 2020
- Accepted Manuscript published: November 9, 2020 (version 1)
- Version of Record published: November 25, 2020 (version 2)
Copyright
© 2020, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Single cell multiomic profiling of human lung reveals cell type-specific and age-dynamic control of SARS-CoV2 host genes
eLife 9:e62522.
https://doi.org/10.7554/eLife.62522
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