Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases
Abstract Human endogenous retroviruses constitute a significant portion of the human genome and play complex roles in gene regulation and disease processes. However, the expression pattern and disease associations of specific retroviral loci remain pooly understood. This study examines the expressio...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62779-7 |
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| _version_ | 1849342662895730688 |
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| author | Fan Zhu Yi Liu Jiehao Lei Xinxing Li Zexu Jiang Xuan Dong Ying Gu Young Li |
| author_facet | Fan Zhu Yi Liu Jiehao Lei Xinxing Li Zexu Jiang Xuan Dong Ying Gu Young Li |
| author_sort | Fan Zhu |
| collection | DOAJ |
| description | Abstract Human endogenous retroviruses constitute a significant portion of the human genome and play complex roles in gene regulation and disease processes. However, the expression pattern and disease associations of specific retroviral loci remain pooly understood. This study examines the expression and regulatory mechanisms of these retroviral elements in immune cells. Utilizing single-cell RNA sequencing data from peripheral blood mononuclear cells, we identify 41,460 expressed retroviral loci, with 1936 showing cell type-specific expression. We further detect 3463 conditionally independent expression quantitative trait loci linked to retroviral elements, highlighting their potential role in mediating genetic variants and disease associations. Notably, these retroviral sequences associate significantly with autoimmune diseases, with specific loci demonstrating pleiotropic associations with disease-related genes. Our findings suggest that these elements are not merely genomic remnants but active participants in cellular regulation and disease progression. This work advances understanding of human-retroviral coevolution and highlights potential therapeutic targets in immune disorders. |
| format | Article |
| id | doaj-art-20c86eb53b4347289aa23f87babb2437 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-20c86eb53b4347289aa23f87babb24372025-08-20T03:43:16ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-62779-7Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseasesFan Zhu0Yi Liu1Jiehao Lei2Xinxing Li3Zexu Jiang4Xuan Dong5Ying Gu6Young Li7BGI ResearchBGI ResearchBGI ResearchBGI ResearchBGI ResearchBGI ResearchBGI ResearchBGI ResearchAbstract Human endogenous retroviruses constitute a significant portion of the human genome and play complex roles in gene regulation and disease processes. However, the expression pattern and disease associations of specific retroviral loci remain pooly understood. This study examines the expression and regulatory mechanisms of these retroviral elements in immune cells. Utilizing single-cell RNA sequencing data from peripheral blood mononuclear cells, we identify 41,460 expressed retroviral loci, with 1936 showing cell type-specific expression. We further detect 3463 conditionally independent expression quantitative trait loci linked to retroviral elements, highlighting their potential role in mediating genetic variants and disease associations. Notably, these retroviral sequences associate significantly with autoimmune diseases, with specific loci demonstrating pleiotropic associations with disease-related genes. Our findings suggest that these elements are not merely genomic remnants but active participants in cellular regulation and disease progression. This work advances understanding of human-retroviral coevolution and highlights potential therapeutic targets in immune disorders.https://doi.org/10.1038/s41467-025-62779-7 |
| spellingShingle | Fan Zhu Yi Liu Jiehao Lei Xinxing Li Zexu Jiang Xuan Dong Ying Gu Young Li Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases Nature Communications |
| title | Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases |
| title_full | Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases |
| title_fullStr | Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases |
| title_full_unstemmed | Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases |
| title_short | Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases |
| title_sort | single cell eqtl mapping of human endogenous retroviruses reveals cell type specific genetic regulation in autoimmune diseases |
| url | https://doi.org/10.1038/s41467-025-62779-7 |
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