Single cell RNA-sequencing of vehicle- and UK5099-treated mouse prostate organoids

The goal of this study was to determine how modulation of mitochondrial pyruvate metabolism regulates gene expression in a three-dimensional organoid model of mouse prostate epithelium. Organoids were treated with the small molecule UK5099, which impairs mitochondrial pyruvate uptake, and subjected to single-cell RNA-sequencing. Our analysis revealed considerable heterogeneity within prostate organoids characterized by distinct cell clusters expressing markers associated with basal, luminal and mesenchymal-like cells. UK5099 treatment led to a reduction in epithelial populations and an enrichment in mesenchymal-like cells. These findings indicate that pyruvate metabolism can modulate features of cell fate in prostate epithelium. Single cell RNA-sequencing of mouse prostate organoids treated with vehicle or UK5099