Single-cell transcriptome reveals cellular heterogeneity and lineage-specific regulatory changes of fibroblasts in post-traumatic urethral stricture.

Fibroblast is the critical repair cell for urethral wound healing. The dysfunction of fibroblasts can lead to excessive fibrosis and hypertrophic scar, which eventually leads to post-traumatic urethral stricture. However, the fibroblast subpopulation and intercellular communication in urethral stricture remains poorly understood. Therefore, a comprehensive single-cell resolution transcript landscape of human PTUS needs to be reported. We performed single-cell RNA-sequencing of 13,411 cells from post-urethral stricture tissue and adjacent normal tissue. Unsupervised clustering, function enrichment analysis, cell trajectory construction and intercellular communication analysis were applied to explore the cellular microenvironment and intercellular communication at single-cell level. We found that there is highly cell heterogeneity in urethral stricture tissue, which includes 11 cell lineages based on the cell markers. We identified the molecular typing of fibroblasts and indicated the key fibroblast subpopulations in the process of fibrogenesis during urethral stricture. The intercellular communication between fibroblasts and vascular endothelial cells was identified. As an important bridge in the communication, integrins may be a potential therapeutic target for post-traumatic urethral stricture. In conclusion, this study reveals the cellular heterogeneity and lineage-specific regulatory changes of fibroblasts in post-traumatic urethral stricture, thereby providing new insights and potential genes for post-traumatic urethral stricture treatment.