Single Cell and Transcriptomic Analysis of Regulatory Mechanisms of Key Genes in Systemic Lupus Erythematosus
Yali Zhou,* Yongzhuo Wu,* Binbin Yang,* Qinghuan Zhu, Haojun Long, Limei Yuan, Wenting Cao, Danqi Deng Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China*These authors contribute...
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| Format: | Article |
| Sprog: | engelsk |
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Dove Medical Press
2025-06-01
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| Serier: | International Journal of General Medicine |
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| Online adgang: | https://www.dovepress.com/single-cell-and-transcriptomic-analysis-of-regulatory-mechanisms-of-ke-peer-reviewed-fulltext-article-IJGM |
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| Summary: | Yali Zhou,* Yongzhuo Wu,* Binbin Yang,* Qinghuan Zhu, Haojun Long, Limei Yuan, Wenting Cao, Danqi Deng Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Danqi Deng, Email danqid128@sina.comBackground: Abnormal cell-mediated immunoregulation plays a central role in the pathogenesis of systemic lupus erythematosus (SLE). Identifying distinct cellular subtypes and key genes is critical for understanding disease mechanisms.Methods: Peripheral blood scRNA-seq was performed on six SLE patients and six controls. The GSE82221 transcriptomic dataset was integrated with scRNA-seq data for a comprehensive analysis. Differentially expressed genes (bulk DEGs) and different immune cells (DICs) were identified from bulk RNA-seq analysis using differential expression and single-sample gene set enrichment analysis (ssGSEA). Key cell populations that showed similar differential patterns to DICs were identified from scRNA-seq data, and a second set of DEGs (single-cell DEGs) was obtained. Key genes were defined as the intersection of bulk and single-cell DEGs with an area under the ROC curve (AUC) > 0.7. Functional enrichment, single-cell expression analysis, methylation analysis, and protein-protein interaction (PPI) network construction were performed on the key genes.Results: From GSE82221, 2041 bulk DEGs and 14 DICs were identified. Memory B cells exhibited consistent differences between SLE and controls in both datasets. Nineteen single-cell DEGs were identified in memory B cells, with six key genes (MX1, IFI44L, ISG15, OAS1, IFI6, IFI27) showing AUC > 0.7. PPI analysis revealed their involvement in antiviral responses. Functional enrichment highlighted pathways such as Epstein–Barr virus infection and NK cell-mediated cytotoxicity. Methylation analysis showed distinct gene regulation patterns, and pseudotime analysis demonstrated dynamic expression of IFI44L and MX1 during B cell differentiation.Conclusion: This study integrated single-cell and bulk transcriptomic data to identify six key genes (MX1, IFI44L, ISG15, OAS1, IFI6, and IFI27) involved in SLE pathogenesis and highlighted the central role of memory B cells. Our findings offer new insights into SLE mechanisms and provide a theoretical basis for developing targeted therapeutic strategies.Keywords: systemic lupus erythematosus, immune cell, key gene, single-cell analysis |
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| ISSN: | 1178-7074 |