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

Area of Science:

• Urology
• Cell Biology
• Immunology

Background:

• Hunner type interstitial cystitis (IC) is a chronic inflammatory bladder condition causing pain and urinary symptoms.
• Understanding the cellular and molecular mechanisms of Hunner IC is crucial for developing targeted therapies.

Purpose of the Study:

• To characterize cellular states and intercellular communication in the bladder microenvironment of Hunner type IC.
• To identify specific cell populations and signaling pathways involved in the pathogenesis of Hunner IC.

Main Methods:

• Single-cell RNA sequencing was performed on Hunner lesions, non-Hunner lesions, and control bladder tissues.
• Analysis focused on identifying distinct cellular populations and their interactions within the bladder microenvironment.

Main Results:

• A neuregulin-enriched fibroblast population was identified and found to be expanded in Hunner lesions.
• These fibroblasts showed enhanced signaling to basal epithelial cells via NRG and WNT pathways.
• Epithelial cells exhibited increased heterogeneity and differentiation towards inflammatory states, indicating tissue remodeling.

Conclusions:

• Hunner type IC involves significant alterations in both stromal and epithelial compartments of the bladder.
• Fibroblast-epithelial communication, particularly involving neuregulin signaling, is a key factor in chronic inflammation and tissue remodeling in Hunner type IC.