Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes
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 ma...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62522 |
| _version_ | 1811236134851706880 |
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| 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 |
| author_facet | 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 |
| author_sort | Allen Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:03:43Z |
| format | Article |
| id | doaj.art-a3ede76a7aec424cbe10045fed11ea98 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:03:43Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a3ede76a7aec424cbe10045fed11ea982022-12-22T03:33:46ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.62522Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genesAllen Wang0https://orcid.org/0000-0001-9870-7888Joshua Chiou1https://orcid.org/0000-0002-4618-0647Olivier B Poirion2Justin Buchanan3Michael J Valdez4Jamie M Verheyden5https://orcid.org/0000-0003-4116-8507Xiaomeng Hou6Parul Kudtarkar7Sharvari Narendra8Jacklyn M Newsome9Minzhe Guo10Dina A Faddah11Kai Zhang12Randee E Young13Justinn Barr14Eniko Sajti15Ravi Misra16Heidie Huyck17Lisa Rogers18Cory Poole19Jeffery A Whitsett20Gloria Pryhuber21Yan Xu22Kyle J Gaulton23https://orcid.org/0000-0003-1318-7161Sebastian Preissl24https://orcid.org/0000-0001-8971-5616Xin Sun25https://orcid.org/0000-0001-8387-4966NHLBI LungMap Consortium26Center for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United StatesBiomedical Sciences Graduate Program, University of California San Diego, La Jolla, United States; Department of Pediatrics, University of California-San Diego, La Jolla, United StatesCenter for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United StatesCenter for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United StatesBiomedical Sciences Graduate Program, University of California San Diego, La Jolla, United States; Department of Pediatrics, University of California-San Diego, La Jolla, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United StatesCenter for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United StatesDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States; Divisions of Pulmonary Biology and Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, United StatesVertex Pharmaceuticals, San Diego, United StatesLudwig Institute for Cancer Research, La Jolla, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United States; Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United StatesDepartment of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United StatesDepartment of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United StatesDepartment of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United StatesDepartment of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United StatesDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States; Divisions of Pulmonary Biology and Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, United StatesDepartment of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United StatesDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States; Divisions of Pulmonary Biology and Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United StatesCenter for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United StatesDepartment of Pediatrics, University of California-San Diego, La Jolla, United States; Department of Biological Sciences, University of California-San Diego, La Jolla, United StatesNIH, Bethesda, United StatesRespiratory 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.https://elifesciences.org/articles/62522lunggene regulationsingle cell RNA/ATAC-seqcis-regulatory elementshuman sequence variantsCOVID-19 |
| spellingShingle | 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 Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes eLife lung gene regulation single cell RNA/ATAC-seq cis-regulatory elements human sequence variants COVID-19 |
| title | Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes |
| title_full | Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes |
| title_fullStr | Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes |
| title_full_unstemmed | Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes |
| title_short | Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes |
| title_sort | single cell multiomic profiling of human lungs reveals cell type specific and age dynamic control of sars cov2 host genes |
| topic | lung gene regulation single cell RNA/ATAC-seq cis-regulatory elements human sequence variants COVID-19 |
| url | https://elifesciences.org/articles/62522 |
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