Single-cell transcriptomics reveal the remodeling landscape of bladder in patients with obstruction-induced detrusor underactivity

Abstract

Detrusor underactivity (DUA) is a common and thorny problem in urology, which severely impairs patients’ bladder function and quality of life. However, its underlying pathophysiological mechanism remains unclear. Hence, we sequenced 69,973 cells from five controls and nine patients with bladder dysfunction using single-cell RNA sequencing. Twelve distinct cell types were identified and they showed high cellular and functional heterogeneity among each group. Among them, fibroblasts, macrophages, and epithelial cells had the most intercellular communications. Their aberrant gene expressions and altered intercellular interactions were mainly involved in extracellular matrix organization, inflammation/immune regulation, and cellular injury. Further re-cluster analysis revealed an accumulation of the RBFOX1⁺ fibroblasts and RIPOR2⁺ macrophages in dysfunctional bladder wall, which mediated bladder remodeling through dysfunctional extracellular matrix organization and inflammation/immune reaction. Besides, the subtype of the epithelial cells was significantly altered. They underwent an intricate process including inflammation, damage, and repair during bladder remodeling. Overall, this work constructed the first single-cell atlas for obstruction-induced DUA, which could provide a valuable resource for deciphering the cellular heterogeneity and function changes in DUA, as well as potential strategies for bladder function improvement.

Keywords

bladder outlet obstruction / bladder remodeling / detrusor underactivity / single-cell RNA sequencing