Cell Genomics (Feb 2023)
Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19
- Bowen Zhang,
- Zhenhua Zhang,
- Valerie A.C.M. Koeken,
- Saumya Kumar,
- Michelle Aillaud,
- Hsin-Chieh Tsay,
- Zhaoli Liu,
- Anke R.M. Kraft,
- Chai Fen Soon,
- Ivan Odak,
- Berislav Bošnjak,
- Anna Vlot,
- Morris A. Swertz,
- Uwe Ohler,
- Robert Geffers,
- Thomas Illig,
- Jochen Huehn,
- Antoine-Emmanuel Saliba,
- Leif Erik Sander,
- Reinhold Förster,
- Cheng-Jian Xu,
- Markus Cornberg,
- Leon N. Schulte,
- Yang Li
Affiliations
- Bowen Zhang
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Beijing Normal University, College of Life Sciences, Beijing, China
- Zhenhua Zhang
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Genomics Coordination Center, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
- Valerie A.C.M. Koeken
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands
- Saumya Kumar
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- Michelle Aillaud
- Institute for Lung Research, Philipps University, Marburg, Germany
- Hsin-Chieh Tsay
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- Zhaoli Liu
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- Anke R.M. Kraft
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung [DZIF]), Partner Site Hannover-Braunschweig, Hannover, Germany; Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany
- Chai Fen Soon
- TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Ivan Odak
- Institute of Immunology, Hannover Medical School, Hannover, Germany
- Berislav Bošnjak
- Institute of Immunology, Hannover Medical School, Hannover, Germany
- Anna Vlot
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Morris A. Swertz
- Genomics Coordination Center, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
- Uwe Ohler
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Robert Geffers
- Genome Analytics, Helmholtz-Center for Infection Research (HZI), Braunschweig, Germany
- Thomas Illig
- German Center for Lung Research (DZL), Giessen, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
- Jochen Huehn
- Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany; Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Antoine-Emmanuel Saliba
- Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Centre for Infection Research (HZI), Wurzburg, Germany
- Leif Erik Sander
- German Center for Lung Research (DZL), Giessen, Germany; Charité–Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany
- Reinhold Förster
- German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung [DZIF]), Partner Site Hannover-Braunschweig, Hannover, Germany; Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany; Institute of Immunology, Hannover Medical School, Hannover, Germany
- Cheng-Jian Xu
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Markus Cornberg
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung [DZIF]), Partner Site Hannover-Braunschweig, Hannover, Germany; Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany
- Leon N. Schulte
- Institute for Lung Research, Philipps University, Marburg, Germany; German Center for Lung Research (DZL), Giessen, Germany
- Yang Li
- Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany; Corresponding author
- Journal volume & issue
-
Vol. 3,
no. 2
p. 100232
Abstract
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe COVID-19 in some patients and mild COVID-19 in others. Dysfunctional innate immune responses have been identified to contribute to COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell multi-omics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified genes that were potentially regulated by differential chromatin accessibility. Then, sub-clustering and motif-enrichment analyses revealed disease condition-specific regulation by transcription factors and their targets, including an interaction between C/EBPs and a long-noncoding RNA LUCAT1, which we validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in COVID-19 patients and identified a SNP rs6800484-C, which is associated with lower expression of CCR2 and may contribute to higher viral loads and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to COVID-19.
