To compare the transurethral surgery outcomes between patients with BOO and obstruction-induced DUA and depict the single-cell transcriptomic atlas of obstruction-induced bladder dysfunction.

We performed a prospective (5 controls, 5 patients with BOO and 4 patients with DUA) and a one-year follow-up to evaluate the outcome of transurethral surgery for obstruction-induced bladder dysfunction. Meanwhile, single-cell RNA sequencing of their bladder tissue and downstream bioinformatics analysis was applied to investigate the change of cellular types and functions in the obstruction-induced DUA.

Both patients with BOO and DUA could have the improvement of symptom and QoL from surgery, although such improvement of DUA seemed inferior to BOO. Through sequencing and analysis, we constructed a single-cell transcriptomic atlas of obstruction-induced bladder dysfunction and identified 12 cell types among total 69973 cells. Cell-cell communication analysis revealed that the fibroblasts and macrophages had the top two intercellular interactions. In the obstruction-induced DUA, the differentially expressed genes and intercellular interactions of fibroblasts were mainly enriched in the extracellular matrix/structure organization. Further re-clustering and subsequent analysis of fibroblasts and macrophages revealed that the dysregulation of cell subtypes and functions might be the underlying trigger for obstruction-induced DUA. As for fibroblasts, fibroblast-3, a subtype whose cell functions were related to fibrosis and terminal type of all fibroblasts, were increased in the remodeled bladder, which indicated that such subtypes could be a critical subtype in the bladder remodeling. Moreover, macrophages could regulate the remodeling through expression of different level of MMP and TIMP genes, which could be an important way for macrophages to regulate fibrosis, instead of M1/2 polarization, in the obstruction-induced DUA.

We found that relieving obstruction by transurethral surgery could be a feasible method to manage obstruction-induced bladder dysfunction and improve patients’ symptom and QoL, although patients who progressed to the phase of DUA could benefit less than those with BOO on the symptom and QoL improvement, which could be the subsequence of obstruction-induced irreversible bladder remodeling. Furtherly, through scRNA-seq, we constructed a comprehensive single-cell transcriptomic atlas of obstruction-induced bladder remodeling and revealed that the essence of obstruction-induced DUA could be a process of inflammation and fibrosis, in which fibroblasts and macrophages were the key cell types. Their subtypes and functions changed from normal to fibrosis-related state might play an important role in the bladder remodeling.

Patients with DUA seemed benefit less on such improvement. As for mechanism underlying it, altered subtypes and functions of fibroblasts and macrophages might mediate bladder dysfunction in the obstruction-induced DUA.

Continence 7S1 (2023) 100970
DOI: 10.1016/j.cont.2023.100970