Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes.

Autor:	Wang A; Center for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United States., Chiou J; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, United States.; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Poirion OB; Center for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United States., Buchanan J; Center for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United States., Valdez MJ; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, United States.; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Verheyden JM; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Hou X; Center for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United States., Kudtarkar P; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Narendra S; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Newsome JM; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Guo M; Division 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 States., Faddah DA; Vertex Pharmaceuticals, San Diego, United States., Zhang K; Ludwig Institute for Cancer Research, La Jolla, United States., Young RE; Department of Pediatrics, University of California-San Diego, La Jolla, United States.; Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States., Barr J; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Sajti E; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Misra R; Department of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United States., Huyck H; Department of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United States., Rogers L; Department of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United States., Poole C; Department of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United States., Whitsett JA; Division 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 States., Pryhuber G; Department of Pediatrics and Clinical & Translational Science Institute, University of Rochester Medical Center, Rochester, United States., Xu Y; Division 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 States., Gaulton KJ; Department of Pediatrics, University of California-San Diego, La Jolla, United States., Preissl S; Center for Epigenomics & Department of Cellular & Molecular Medicine, University of California, San Diego, San Diego, United States., Sun X; Department of Pediatrics, University of California-San Diego, La Jolla, United States.; Department of Biological Sciences, University of California-San Diego, La Jolla, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Nov 09; Vol. 9. Date of Electronic Publication: 2020 Nov 09.
DOI:	10.7554/eLife.62522
Abstrakt:	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. Competing Interests: AW, JC, OP, JB, MV, JV, XH, PK, SN, JN, MG, KZ, RY, JB, ES, RM, HH, LR, CP, JW, GP, YX, SP, XS No competing interests declared, DF employee of and holds stock in Vertex Pharmaceuticals, KG does consulting for Genentech (© 2020, Wang et al.)
Databáze:	MEDLINE
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