Single Cell and Transcriptomic Analysis of Regulatory Mechanisms of Key Genes in Systemic Lupus Erythematosus
Yali Zhou1, Yongzhuo Wu1, Binbin Yang1
1Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
Background:
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.
