Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19
| Autor: | 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 |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI) |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
allele-specific open chromatin
Cancer Research All institutes and research themes of the Radboud University Medical Center scRNA-seq Genetics lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] COVID-19 scATAC-seq Biochemistry Genetics and Molecular Biology (miscellaneous) epigenetic regulation genetic regulation |
| Zdroj: | Cell Genomics, 3(2):100232 Cell Genomics, 3, 2 Cell Genomics, 3 |
| ISSN: | 2666-979X |
| Popis: | Contains fulltext : 290824.pdf (Publisher’s version ) (Open Access) 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. |
| Databáze: | OpenAIRE |
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