Single-cell atlas of urethral stricture reveals fibroblast, mast cell, and macrophage heterogeneity with candidate regulators
- 1Department of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University
- 2Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University
Abstract
Background: Urethral strictures are characterized by fibrotic scar tissue formation in the urethra, leading to difficulties in urination and potential renal dysfunction. The cellular microenvironment contributes to stenosis. However, the heterogeneity of key cell types hinders our understanding of this disease.
Methods: Single-cell RNA sequencing was performed on three urethral scar tissues and three normal urethral tissues. First, the main cell types and sample heterogeneity were identified. Transcription factor (TF) and enrichment analyses were used to characterize the transcriptional regulation and metabolic patterns of fibroblasts and mast cells. Finally, CellChat was used to elucidate intercellular communication networks in urethral scar tissues.
Results: Of the eight cell types detected, fibroblasts, mast cells, and macrophages were major contributors to urethral scar tissue. These cells were categorized into seven (FB0–FB6), two (Mast0 and Mast1), and nine (Macro0-Macro8) subclusters, respectively, based on heterogeneity. Urethral scar tissue exhibited increased proportions of FB3 fibroblast, Mast1 mast cell, Macro1, and Macro7 Macrophages. Marker genes of these subclusters were associated with fibrosis-related biological processes, including cell adhesion and extracellular matrix organization. Additionally, screening of the dysregulation of multiple TFs and metabolic pathways revealed potential candidate TFs—ETS1 (from FB3) and SMAD3 (from Mast1)—associated with fibrosis. Furthermore, communication substantially increased between fibroblasts and other cells, and between Macro1 or Macro7 and other macrophage subclusters or fibroblasts in urethral scar tissue.
Conclusions: We revealed the transcriptional characteristics of candidate cells involved in the fibrogenesis of urethral stricture, which provides insights into the pathogenesis of urethral stenosis and may facilitate the exploration of therapeutic targets.
Related
- CAR-macrophage immunotherapy targeting fibroblast-like synoviocytes ameliorates inflammatory and degenerative arthritis
- Transcriptional differences between repeatedly recultured and freshly induced embryogenic calli reveal candidate developmental regulators
- A single-cell atlas of pediatric undifferentiated recurrent fever reveals candidate immune regulators
- Multi-omics reveals a monocyte-macrophage-fibroblast axis in post-COVID-19 fibroinflammatory lung remodelling
- Spatial macrophage-fibroblast interactions in osteoarthritis synovium: inflammatory and fibrotic niches
BibTeX
@article{chong2026singlecell,
title = {{Single-cell atlas of urethral stricture reveals fibroblast, mast cell, and macrophage heterogeneity with candidate regulators}},
author = {Yue Chong and Jun Zhao and Zhenlong Wang and Delai Fu and Xiaoqiang Zhai and Linlin Zhang and Hong Wang and Mei Gao and Yu Qiao and Mingrui Li and Li Xue and Tie Chong},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1932042},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932042/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell atlas of urethral stricture reveals fibroblast, mast cell, and macrophage heterogeneity with candidate regulators
AU - Yue Chong
AU - Jun Zhao
AU - Zhenlong Wang
AU - Delai Fu
AU - Xiaoqiang Zhai
AU - Linlin Zhang
AU - Hong Wang
AU - Mei Gao
AU - Yu Qiao
AU - Mingrui Li
AU - Li Xue
AU - Tie Chong
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1932042
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932042/full
AB - Background: Urethral strictures are characterized by fibrotic scar tissue formation in the urethra, leading to difficulties in urination and potential renal dysfunction. The cellular microenvironment contributes to stenosis. However, the heterogeneity of key cell types hinders our understanding of this disease. Methods: Single-cell RNA sequencing was performed on three urethral scar tissues and three normal urethral tissues. First, the main cell types and sample heterogeneity were identified. Transcription factor (TF) and enrichment analyses were used to characterize the transcriptional regulation and metabolic patterns of fibroblasts and mast cells. Finally, CellChat was used to elucidate intercellular communication networks in urethral scar tissues. Results: Of the eight cell types detected, fibroblasts, mast cells, and macrophages were major contributors to urethral scar tissue. These cells were categorized into seven (FB0–FB6), two (Mast0 and Mast1), and nine (Macro0-Macro8) subclusters, respectively, based on heterogeneity. Urethral scar tissue exhibited increased proportions of FB3 fibroblast, Mast1 mast cell, Macro1, and Macro7 Macrophages. Marker genes of these subclusters were associated with fibrosis-related biological processes, including cell adhesion and extracellular matrix organization. Additionally, screening of the dysregulation of multiple TFs and metabolic pathways revealed potential candidate TFs—ETS1 (from FB3) and SMAD3 (from Mast1)—associated with fibrosis. Furthermore, communication substantially increased between fibroblasts and other cells, and between Macro1 or Macro7 and other macrophage subclusters or fibroblasts in urethral scar tissue. Conclusions: We revealed the transcriptional characteristics of candidate cells involved in the fibrogenesis of urethral stricture, which provides insights into the pathogenesis of urethral stenosis and may facilitate the exploration of therapeutic targets.
SN - 1664-3224
ER -