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.
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.
- Allen Wang
- Jamie M Verheyden
- Sebastian Preissl
- Xin Sun
- Gloria Pryhuber
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Edward E Morrisey, University of Pennsylvania, United States
© 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.