Kuret Tadeja, Kreft Mateja Erdani
Institute of Cell Biology, Faculty of Medicine University of Ljubljana Ljubljana Slovenia.
BJUI Compass. 2025 Aug 4;6(8):e70051. doi: 10.1002/bco2.70051. eCollection 2025 Aug.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disorder with unknown aetiology and limited treatment options. Single-cell RNA-sequencing (scRNA-seq) has provided unprecedented insights into cellular heterogeneity in IC/BPS. This review summarizes recent scRNA-seq findings on bladder cell populations, emphasizing urothelial, interstitial and immune cells.
A comprehensive analysis of published scRNA-seq studies was conducted to compare bladder cell subtypes in healthy and IC/BPS-affected bladders. Differences between IC/BPS patients and mouse models, as well as sex-specific cellular variations, were examined.
IC/BPS bladders exhibit significant urothelial alterations, including a reduction in UPK3A + umbrella cells and an expansion of progenitor-like cells with impaired regenerative capacity, linked to TLR3-NR2F6 signalling. Interstitial cells include three fibroblast subtypes (PDGFRA+, RGS5+ and pro-inflammatory IL6-producing fibroblasts), which contribute to fibrosis and inflammation. The immune landscape is characterized by a Th1-biased response, exhausted CD8 + T cells and reduced regulatory T cells, with HPV infection detected in most IC/BPS patients, suggesting a possible viral aetiology. Cell-to-cell interactions are compromised, with enhanced macrophage-endothelial signalling via CXCL8-ACKR1 and CXCL2/3-ACKR1 pathways, highlighting potential therapeutic targets. Notably, sex-based differences reveal stronger immune activation in females and increased urothelial proliferation in males, potentially explaining the higher IC/BPS prevalence in females.
scRNA-seq has advanced our understanding of IC/BPS by identifying disease-associated cell types, signalling pathways and intercellular interactions. Future research should integrate multi-omics approaches and explore non-invasive urine-based scRNA-seq for improved diagnosis and therapy.
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）是一种病因不明且治疗选择有限的慢性炎症性膀胱疾病。单细胞RNA测序（scRNA-seq）为IC/BPS中的细胞异质性提供了前所未有的见解。本综述总结了最近关于膀胱细胞群体的scRNA-seq研究结果，重点关注尿路上皮细胞、间质细胞和免疫细胞。
对已发表的scRNA-seq研究进行综合分析，以比较健康膀胱和受IC/BPS影响的膀胱中的膀胱细胞亚型。研究了IC/BPS患者与小鼠模型之间的差异以及性别特异性细胞差异。
IC/BPS膀胱表现出明显的尿路上皮改变，包括UPK3A + 伞细胞减少和再生能力受损的祖细胞样细胞扩增，这与TLR3-NR2F6信号传导有关。间质细胞包括三种成纤维细胞亚型（PDGFRA +、RGS5 + 和产生促炎IL6的成纤维细胞），它们促成纤维化和炎症。免疫格局的特征是Th1偏向性反应、耗竭的CD8 + T细胞和调节性T细胞减少，大多数IC/BPS患者检测到HPV感染，提示可能的病毒病因。细胞间相互作用受损，通过CXCL8-ACKR1和CXCL2/3-ACKR1途径增强巨噬细胞-内皮细胞信号传导，突出了潜在的治疗靶点。值得注意的是，基于性别的差异显示女性免疫激活更强，男性尿路上皮增殖增加，这可能解释了女性中IC/BPS患病率较高的原因。
scRNA-seq通过识别与疾病相关的细胞类型、信号通路和细胞间相互作用，推进了我们对IC/BPS的理解。未来的研究应整合多组学方法，并探索基于尿液的非侵入性scRNA-seq以改善诊断和治疗。
