Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis
BackgroundSystemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1212330/full |
| _version_ | 1797399508432191488 |
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| author | Yanling Cui Yanling Cui Huina Zhang Huina Zhang Zhen Wang Zhen Wang Bangdong Gong Hisham Al-Ward Hisham Al-Ward Yaxuan Deng Yaxuan Deng Orion Fan Orion Fan Junbang Wang Wenmin Zhu Yi Eve Sun Yi Eve Sun |
| author_facet | Yanling Cui Yanling Cui Huina Zhang Huina Zhang Zhen Wang Zhen Wang Bangdong Gong Hisham Al-Ward Hisham Al-Ward Yaxuan Deng Yaxuan Deng Orion Fan Orion Fan Junbang Wang Wenmin Zhu Yi Eve Sun Yi Eve Sun |
| author_sort | Yanling Cui |
| collection | DOAJ |
| description | BackgroundSystemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE and pSS.MethodsGene expression profiles of SLE and pSS were obtained from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify shared genes related to SLE and pSS. Overlapping genes were then subject to Gene Ontology (GO) and protein-protein interaction (PPI) network analyses. Cytoscape plugins cytoHubba and iRegulon were subsequently used to screen shared hub genes and predict TFs. In addition, gene set variation analysis (GSVA) and CIBERSORTx were used to calculate the correlations between hub genes and immune cells as well as related pathways. To confirm these results, hub genes and TFs were verified in microarray and single-cell RNA sequencing (scRNA-seq) datasets.ResultsFollowing WGCNA and limma analysis, 152 shared genes were identified. These genes were involved in interferon (IFN) response and cytokine-mediated signaling pathway. Moreover, we screened six shared genes, namely IFI44L, ISG15, IFIT1, USP18, RSAD2 and ITGB2, out of which three genes, namely IFI44L, ISG15 and ITGB2 were found to be highly expressed in both microarray and scRNA-seq datasets. IFN response and ITGB2 signaling pathway were identified as potentially relevant pathways. In addition, STAT1 and IRF7 were identified as common TFs in both diseases.ConclusionThis study revealed IFI44L, ISG15 and ITGB2 as the shared genes and identified STAT1 and IRF7 as the common TFs of SLE and pSS. Notably, the IFN response and ITGB2 signaling pathway played vital roles in both diseases. Our study revealed common pathogenetic characteristics of SLE and pSS. The particular roles of these pivotal genes and mutually overlapping pathways may provide a basis for further mechanistic research. |
| first_indexed | 2024-03-09T01:40:17Z |
| format | Article |
| id | doaj.art-999e6502912645ea9e96b0947533cd61 |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T01:40:17Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-999e6502912645ea9e96b0947533cd612023-12-08T16:05:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12123301212330Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysisYanling Cui0Yanling Cui1Huina Zhang2Huina Zhang3Zhen Wang4Zhen Wang5Bangdong Gong6Hisham Al-Ward7Hisham Al-Ward8Yaxuan Deng9Yaxuan Deng10Orion Fan11Orion Fan12Junbang Wang13Wenmin Zhu14Yi Eve Sun15Yi Eve Sun16Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDivision of Rheumatology, Tongji Hospital of Tongji University School of Medicine, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaBackgroundSystemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE and pSS.MethodsGene expression profiles of SLE and pSS were obtained from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify shared genes related to SLE and pSS. Overlapping genes were then subject to Gene Ontology (GO) and protein-protein interaction (PPI) network analyses. Cytoscape plugins cytoHubba and iRegulon were subsequently used to screen shared hub genes and predict TFs. In addition, gene set variation analysis (GSVA) and CIBERSORTx were used to calculate the correlations between hub genes and immune cells as well as related pathways. To confirm these results, hub genes and TFs were verified in microarray and single-cell RNA sequencing (scRNA-seq) datasets.ResultsFollowing WGCNA and limma analysis, 152 shared genes were identified. These genes were involved in interferon (IFN) response and cytokine-mediated signaling pathway. Moreover, we screened six shared genes, namely IFI44L, ISG15, IFIT1, USP18, RSAD2 and ITGB2, out of which three genes, namely IFI44L, ISG15 and ITGB2 were found to be highly expressed in both microarray and scRNA-seq datasets. IFN response and ITGB2 signaling pathway were identified as potentially relevant pathways. In addition, STAT1 and IRF7 were identified as common TFs in both diseases.ConclusionThis study revealed IFI44L, ISG15 and ITGB2 as the shared genes and identified STAT1 and IRF7 as the common TFs of SLE and pSS. Notably, the IFN response and ITGB2 signaling pathway played vital roles in both diseases. Our study revealed common pathogenetic characteristics of SLE and pSS. The particular roles of these pivotal genes and mutually overlapping pathways may provide a basis for further mechanistic research.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1212330/fullsystemic lupus erythematosusprimary Sjögren’s syndromebioinformaticshub genesTFsscRNA-seq |
| spellingShingle | Yanling Cui Yanling Cui Huina Zhang Huina Zhang Zhen Wang Zhen Wang Bangdong Gong Hisham Al-Ward Hisham Al-Ward Yaxuan Deng Yaxuan Deng Orion Fan Orion Fan Junbang Wang Wenmin Zhu Yi Eve Sun Yi Eve Sun Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis Frontiers in Immunology systemic lupus erythematosus primary Sjögren’s syndrome bioinformatics hub genes TFs scRNA-seq |
| title | Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis |
| title_full | Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis |
| title_fullStr | Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis |
| title_full_unstemmed | Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis |
| title_short | Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis |
| title_sort | exploring the shared molecular mechanisms between systemic lupus erythematosus and primary sjogren s syndrome based on integrated bioinformatics and single cell rna seq analysis |
| topic | systemic lupus erythematosus primary Sjögren’s syndrome bioinformatics hub genes TFs scRNA-seq |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1212330/full |
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