Using organoid xenograft model of PKD to validate novel pathological pathways revealed by single cell analysis

Abstract

PKD is a major global health concern, contributing significantly to end-stage renal disease. Current therapeutic challenges in PKD stem from its complex pathogenesis, requiring extensive research to identify effective targets and unravel signaling networks. While notable advances have been made using animal and cell models, it is crucial to validate findings in human-relevant models for practical applications. Recent studies with human kidney organoids for PKD modeling have demonstrated promising results, successfully developing tubular cysts in vitro. Despite these achievements, a research gap exists in the comprehensive single-cell resolution analysis of PKD organoids and their comparison to patient samples. Addressing this gap, we conducted single-cell analysis to explore pathological pathways associated with cystogenesis in PKD organoids, aiming to enhance understanding from tissue to transcriptomic levels and promote potential targeted therapeutic interventions. Furthermore, we enhanced the practical impact of our findings by validating these pathways through an in vivo organoid xenograft model.