Single-cell profiling defines the cellular landscape of the urinary bladder: a scoping review

BACKGROUND: The urinary bladder contains a heterogeneous cell population. Multiple studies utilizing single-cell RNA sequencing techniques have uncovered the complex transcriptomic profile of cells in the healthy bladder.

OBJECTIVE: The present study aims to map existing evidence on the use of single-cell RNA sequencing to assess cellular heterogeneity in the healthy urinary bladder and to identify gaps in the literature that could guide future research.

DESIGN: We searched four online databases, supplemented with manual searches, to identify relevant studies that characterized various cell types of the bladder at single-cell resolution. Studies that did not meet the predefined inclusion criteria were excluded based on a protocol drafted a priori. We included only studies published in English.

RESULTS: Twelve studies met the inclusion criteria, investigating various subtypes of cells: urothelial, interstitial, smooth muscle, immune, endothelial, mesothelial, and neural. A landmark study differentiating mural cells from fibroblasts was also presented. Another study compared the use of single-cell with single-nuclei RNA sequencing to assess the utility of the latter for cell identification. We further discussed the gaps and requirements necessary to implement single-cell RNA sequencing in a clinical setting.

CONCLUSION: The combined results highlight several rare and newly identified cell types in different compartments of the urinary bladder. Data integration and validation across multiple modalities are critical steps forward to resolve the cellular complexity of the urinary bladder.