Single-cell transcriptomics reveals bladder microenvironment dynamics in Hunner type interstitial cystitis.

Hunner type interstitial cystitis is a chronic inflammatory bladder disorder characterized by pain and severe lower urinary tract symptoms. Using single-cell RNA sequencing of Hunner lesions, non-Hunner lesions, and control bladder tissues, we characterized cellular states and intercellular communication within the bladder microenvironment. We identified a neuregulin enriched fibroblast population that was preferentially expanded in Hunner lesions and exhibited enhanced signaling toward basal epithelial cells through NRG and WNT pathways. In contrast, myofibroblast states were more prominent in non-Hunner lesions. Epithelial cells showed increased heterogeneity and differentiation toward inflammatory umbrella cell states, consistent with tissue remodeling. These findings define stromal and epithelial alterations across the diseased bladder and highlight fibroblast epithelial communication as a potential contributor to chronic inflammation and tissue remodeling in Hunner type interstitial cystitis.