{"title":"单细胞RNA测序揭示了人类输尿管瘢痕狭窄组织的细胞异质性和微环境重塑。","authors":"Xiaobo Ding, Guoxiang Li, Yuehan Yang, Zhengyao Song, Xudong Shen, Bingbing Hou, Meng Zhang, Shifang Sang, Jian Dai, Jiankang Zhang, Zongyao Hao, Yang Chen, Chaozhao Liang","doi":"10.2147/JIR.S540340","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to construct a comprehensive single-cell transcriptomic atlas of human ureteral scar stricture tissue using single-cell RNA sequencing (scRNA-seq), to uncover cellular heterogeneity, subpopulation dynamics, and intercellular communication networks.</p><p><strong>Methods: </strong>Ureteral tissues were collected from three normal controls (CTR) and three patients with ureteral scar stricture (US). Single-cell suspensions were prepared using the MobiNova-100 platform and sequenced on the Illumina NovaSeq 6000 system. Data were analyzed using Seurat, Harmony, Monocle2 (for pseudotime trajectory analysis), CellChat (for cell-cell communication), and SCP (for GO/KEGG enrichment). Key findings were validated by multiplex immunofluorescence (IF) and immunohistochemistry (IHC).</p><p><strong>Results: </strong>Eleven major cell types were identified, including epithelial, stromal, endothelial, and immune cells, each comprising distinct subpopulations. Compared to CTR tissues, US tissues exhibited an increased proportion of S100A8<sup>+</sup> and MT1E<sup>+</sup> basal epithelial cells with pro-inflammatory characteristics. Fibroblasts displayed substantial heterogeneity, with expansion of inflammatory fibroblasts and smooth muscle cell subsets. Endothelial cells (ECs) showed upregulated inflammatory and antigen presentation pathways. Macrophages exhibited mixed M1/M2 polarization, with enrichment of APOE<sup>+</sup> and APOBEC3A<sup>+</sup> subsets. Additionally, Th17, Treg, and CD8<sup>+</sup> T cell populations were elevated. Cell-cell communication analysis revealed enhanced signaling among fibroblasts, ECs, and immune subsets, particularly via PERIOSTIN, collagen, and laminin pathways.</p><p><strong>Conclusion: </strong>This study presents the first high-resolution single-cell atlas of ureteral scar stricture tissue, revealing profound cellular heterogeneity and remodeling of the immune-stromal-epithelial landscape. The findings also highlight intensified intercellular communication within the fibrotic microenvironment, offering novel insights into disease pathogenesis and potential therapeutic targets.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12749-12768"},"PeriodicalIF":4.1000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449274/pdf/","citationCount":"0","resultStr":"{\"title\":\"Single-Cell RNA Sequencing Reveals Cellular Heterogeneity and Microenvironmental Remodeling in Human Ureteral Scar Stricture Tissue.\",\"authors\":\"Xiaobo Ding, Guoxiang Li, Yuehan Yang, Zhengyao Song, Xudong Shen, Bingbing Hou, Meng Zhang, Shifang Sang, Jian Dai, Jiankang Zhang, Zongyao Hao, Yang Chen, Chaozhao Liang\",\"doi\":\"10.2147/JIR.S540340\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This study aimed to construct a comprehensive single-cell transcriptomic atlas of human ureteral scar stricture tissue using single-cell RNA sequencing (scRNA-seq), to uncover cellular heterogeneity, subpopulation dynamics, and intercellular communication networks.</p><p><strong>Methods: </strong>Ureteral tissues were collected from three normal controls (CTR) and three patients with ureteral scar stricture (US). Single-cell suspensions were prepared using the MobiNova-100 platform and sequenced on the Illumina NovaSeq 6000 system. Data were analyzed using Seurat, Harmony, Monocle2 (for pseudotime trajectory analysis), CellChat (for cell-cell communication), and SCP (for GO/KEGG enrichment). Key findings were validated by multiplex immunofluorescence (IF) and immunohistochemistry (IHC).</p><p><strong>Results: </strong>Eleven major cell types were identified, including epithelial, stromal, endothelial, and immune cells, each comprising distinct subpopulations. Compared to CTR tissues, US tissues exhibited an increased proportion of S100A8<sup>+</sup> and MT1E<sup>+</sup> basal epithelial cells with pro-inflammatory characteristics. Fibroblasts displayed substantial heterogeneity, with expansion of inflammatory fibroblasts and smooth muscle cell subsets. Endothelial cells (ECs) showed upregulated inflammatory and antigen presentation pathways. Macrophages exhibited mixed M1/M2 polarization, with enrichment of APOE<sup>+</sup> and APOBEC3A<sup>+</sup> subsets. Additionally, Th17, Treg, and CD8<sup>+</sup> T cell populations were elevated. Cell-cell communication analysis revealed enhanced signaling among fibroblasts, ECs, and immune subsets, particularly via PERIOSTIN, collagen, and laminin pathways.</p><p><strong>Conclusion: </strong>This study presents the first high-resolution single-cell atlas of ureteral scar stricture tissue, revealing profound cellular heterogeneity and remodeling of the immune-stromal-epithelial landscape. The findings also highlight intensified intercellular communication within the fibrotic microenvironment, offering novel insights into disease pathogenesis and potential therapeutic targets.</p>\",\"PeriodicalId\":16107,\"journal\":{\"name\":\"Journal of Inflammation Research\",\"volume\":\"18 \",\"pages\":\"12749-12768\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449274/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inflammation Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/JIR.S540340\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JIR.S540340","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Single-Cell RNA Sequencing Reveals Cellular Heterogeneity and Microenvironmental Remodeling in Human Ureteral Scar Stricture Tissue.
Purpose: This study aimed to construct a comprehensive single-cell transcriptomic atlas of human ureteral scar stricture tissue using single-cell RNA sequencing (scRNA-seq), to uncover cellular heterogeneity, subpopulation dynamics, and intercellular communication networks.
Methods: Ureteral tissues were collected from three normal controls (CTR) and three patients with ureteral scar stricture (US). Single-cell suspensions were prepared using the MobiNova-100 platform and sequenced on the Illumina NovaSeq 6000 system. Data were analyzed using Seurat, Harmony, Monocle2 (for pseudotime trajectory analysis), CellChat (for cell-cell communication), and SCP (for GO/KEGG enrichment). Key findings were validated by multiplex immunofluorescence (IF) and immunohistochemistry (IHC).
Results: Eleven major cell types were identified, including epithelial, stromal, endothelial, and immune cells, each comprising distinct subpopulations. Compared to CTR tissues, US tissues exhibited an increased proportion of S100A8+ and MT1E+ basal epithelial cells with pro-inflammatory characteristics. Fibroblasts displayed substantial heterogeneity, with expansion of inflammatory fibroblasts and smooth muscle cell subsets. Endothelial cells (ECs) showed upregulated inflammatory and antigen presentation pathways. Macrophages exhibited mixed M1/M2 polarization, with enrichment of APOE+ and APOBEC3A+ subsets. Additionally, Th17, Treg, and CD8+ T cell populations were elevated. Cell-cell communication analysis revealed enhanced signaling among fibroblasts, ECs, and immune subsets, particularly via PERIOSTIN, collagen, and laminin pathways.
Conclusion: This study presents the first high-resolution single-cell atlas of ureteral scar stricture tissue, revealing profound cellular heterogeneity and remodeling of the immune-stromal-epithelial landscape. The findings also highlight intensified intercellular communication within the fibrotic microenvironment, offering novel insights into disease pathogenesis and potential therapeutic targets.
期刊介绍：
An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
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