Single-cell transcriptomics reveals bladder microenvironment dynamics in Hunner type interstitial cystitis
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Summary 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. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.jpg undfig1 anchor portrait graphical abs0015 Highlights • Single-cell transcriptomics maps cellular states in Hunner type IC u0010 • NRG enriched fibroblasts are expanded in Hunner lesions u0015 • Fibroblast epithelial signaling is enhanced through NRG and WNT pathways u0020 • Epithelial and immune heterogeneity increases with disease progression u0025 simple ulist0010 author-highlights abs0020 Immun
Abstract
Summary 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. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.jpg undfig1 anchor portrait graphical abs0015 Highlights • Single-cell transcriptomics maps cellular states in Hunner type IC u0010 • NRG enriched fibroblasts are expanded in Hunner lesions u0015 • Fibroblast epithelial signaling is enhanced through NRG and WNT pathways u0020 • Epithelial and immune heterogeneity increases with disease progression u0025 simple ulist0010 author-highlights abs0020 Immunology; Pathology; Genomics; Transcriptomics teaser abs0025