학술논문
Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes
Document Type
article
Author
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
Source
eLife, Vol 9 (2020)
Subject
Language
English
ISSN
2050-084X
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.