Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes
Updated October 20, 2023Respiratory 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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Analysis Portals
Project Label
Human_Multiome-Lung-Lifespan-UCSD1Species
Sample Type
Anatomical Entity
Organ Part
Selected Cell Types
Disease Status (Specimen)
Disease Status (Donor)
Development Stage
Library Construction Method
Nucleic Acid Source
Paired End
trueAnalysis Protocol
0b4eeed3-20be-4bd6-9a4f-0a6c3fe0fb25, c9d53f42-2afb-4b4f-baeb-fd881a51489eFile Format
Cell Count Estimate
UnspecifiedDonor Count
10