| 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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Cell Genomics, Vol 3, Iss 2, Pp 100232- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2666-979X |
| DOI: |
10.1016/j.xgen.2022.100232 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
