New insights into interstitial cystitis/bladder pain syndrome at single-cell resolution

Kuret, Tadeja (author), Erdani-Kreft, Mateja (author)

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

• Language: English
• Keywords: bladder pain syndrome, high throughput, immune cells, interstitial cells, interstitial cystitis, single-cell landscape, urothelial cells
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 11 str.
• Numbering: Vol. 6, iss. 8, art. e70051
• PID: 20.500.12556/RUL-176186
• UDC: 576
• ISSN on article: 2688-4526
• DOI: 10.1002/bco2.70051
• COBISS.SI-ID: 246837251
• Publication date in RUL: 24.11.2025

Record is a part of a journal

• Title: BJUI compass
• Shortened title: BJUI compass
• Publisher: Wiley, BJU International
• ISSN: 2688-4526
• COBISS.SI-ID: 56356099

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: sindrom bolečine v mehurju, visoka prepustnost, imunske celice, intersticijske celice, intersticijski cistitis, urotelijske celice

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: Z3-50118
• Name: Raziskovanje mehanizmov povezave med oksidativnim stresom in kroničnim vnetjem pri intersticijskem cistitisu/sindromu bolečega mehurja

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0108
• Name: Celična biologija in molekularna genetika v biomedicini