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| Item Type: | Article |
|---|---|
| Title: | Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19 |
| Creators Name: | Zhang, B., Zhang, Z., Koeken, V.A.C.M., Kumar, S., Aillaud, M., Tsay, H.C., Liu, Z., Kraft, A.R.M., Soon, C.F., Odak, I., Bošnjak, B., Vlot, A., Swertz, M.A., Ohler, U., Geffers, R., Illig, T., Huehn, J., Saliba, A.E., Sander, L.E., Förster, R., Xu, C.J., Cornberg, M., Schulte, L.N. and Li, Y. |
| Abstract: | SARS-CoV-2 infection causes severe COVID-19 in some patients and mild 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 reveals 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. |
| Source: | Cell Genomics |
| ISSN: | 2666-979X |
| Publisher: | Cell Press |
| Volume: | 3 |
| Number: | 2 |
| Page Range: | 100232 |
| Date: | 8 February 2023 |
| Official Publication: | https://doi.org/10.1016/j.xgen.2022.100232 |
| PubMed: | View item in PubMed |
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