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已发表论文
单细胞 RNA 测序揭示了人类输尿管瘢痕狭窄组织中的细胞异质性和微环境重塑
Authors Ding X, Li G, Yang Y, Song Z, Shen X, Hou B, Zhang M , Sang S, Dai J, Zhang J, Hao Z, Chen Y, Liang C
Received 14 May 2025
Accepted for publication 28 August 2025
Published 15 September 2025 Volume 2025:18 Pages 12749—12768
DOI https://doi.org/10.2147/JIR.S540340
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Wenjian Li
Xiaobo Ding,1– 4,* Guoxiang Li,1– 3,* Yuehan Yang,1– 3,* Zhengyao Song,1– 3 Xudong Shen,1– 3 Bingbing Hou,1– 3 Meng Zhang,1– 3 Shifang Sang,4 Jian Dai,5 Jiankang Zhang,6 Zongyao Hao,1– 3 Yang Chen,1– 3 Chaozhao Liang1– 3
1Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Institute of Urology, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Urology, Lu’an People’s Hospital of Anhui Province, Lu’an, Anhui, People’s Republic of China; 5Department of Otorhinolaryngology, Lu’an People’s Hospital of Anhui Province, Lu’an, Anhui, People’s Republic of China; 6Department of Infectious Diseases, Lu’an People’s Hospital of Anhui Province, Lu’an, Anhui, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yang Chen, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Email douxing20210107@163.com Chaozhao Liang, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel/Fax +86 55162922234, Email liang_chaozhao@ahmu.edu.cn
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.
Keywords: ureteral stricture, single-cell rna sequencing, cell-cell communication, immune microenvironment
1Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Institute of Urology, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Urology, Lu’an People’s Hospital of Anhui Province, Lu’an, Anhui, People’s Republic of China; 5Department of Otorhinolaryngology, Lu’an People’s Hospital of Anhui Province, Lu’an, Anhui, People’s Republic of China; 6Department of Infectious Diseases, Lu’an People’s Hospital of Anhui Province, Lu’an, Anhui, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yang Chen, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Email douxing20210107@163.com Chaozhao Liang, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel/Fax +86 55162922234, Email liang_chaozhao@ahmu.edu.cn
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.
Keywords: ureteral stricture, single-cell rna sequencing, cell-cell communication, immune microenvironment