GSE168733
Single-cell RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer [scRNA-seq 2]
Prostate cancer is heterogeneous and patients would benefit from methods that stratify clinically indolent from more aggressive forms of the disease. We employed single-cell RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified pre-existing and treatment-persistent cell subpopulations that possess transcriptional stem-like features and regenerative potential when subjected to treatment. We found distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent stem-like cells were able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal hitherto unrecognized molecular predictors of treatment response. This suggests that high analytical resolution of pre-clinical models may powerfully inform clinical decision-making. Overall design: Single-cell RNA sequencing of LNCaP cells treated with 10µM enzalutamide for 168 hours, VCaP parental cells (treated with DMSO for 48 hours), and VCaP cells treated with 10µM enzalutamide for 48 hours.