Li Kuiqing, Lai Cong, Hei Shangyan, Liu Cheng, Li Zhuohang, Kewei Xu
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Traditional Chinese Medicine Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Biochem Biophys Rep. 2023 Jan 23;33:101431. doi: 10.1016/j.bbrep.2023.101431. eCollection 2023 Mar.
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.
成纤维细胞是尿道伤口愈合的关键修复细胞。成纤维细胞功能障碍可导致过度纤维化和肥厚性瘢痕，最终导致创伤后尿道狭窄。然而，尿道狭窄中成纤维细胞亚群和细胞间通讯仍知之甚少。因此，需要报道一份全面的人类创伤后尿道狭窄单细胞分辨率转录图谱。我们对来自尿道狭窄组织和相邻正常组织的13411个细胞进行了单细胞RNA测序。应用无监督聚类、功能富集分析、细胞轨迹构建和细胞间通讯分析，在单细胞水平上探索细胞微环境和细胞间通讯。我们发现尿道狭窄组织中存在高度的细胞异质性，根据细胞标志物可分为11个细胞谱系。我们确定了成纤维细胞的分子分型，并指出了尿道狭窄纤维化过程中关键的成纤维细胞亚群。确定了成纤维细胞与血管内皮细胞之间的细胞间通讯。作为通讯中的重要桥梁，整合素可能是创伤后尿道狭窄的潜在治疗靶点。总之，本研究揭示了创伤后尿道狭窄中成纤维细胞的细胞异质性和谱系特异性调控变化，从而为创伤后尿道狭窄治疗提供了新的见解和潜在基因。
