LAUSR

Introduction: Recent studies have shown that cells undergoing oncogenic processes usurp normal developmental pathways to escape regulators of unsolicited growth. Basal to luminal differentiation in the prostate serves as another cellular process that can go awry, the dysregulation of which can enable oncogenesis in the prostate. Studies have found bi-potent cells in prostate epithelium and speculate those to be cells of origin in prostate cancer. Methods and Results: Through single-cell RNA sequencing we investigated basal to luminal differentiation of normal human prostate epithelial cells across timepoints Days 0, 4, 8, 12, 16, and 20 by stimulating with FGF-7 (20ng/mL) and R1881 (10nM) and explored the data to identify unique populations present in the differentiation process. Our results show spatial separation at various timepoints with distinct transcriptomics profile at Day 0, Day 16, and Day 20. As expected, populations present at Day 0 are also present across all timepoint, though enrichment of various distinct populations emerged throughout the differentiation process. Using trajectory analysis (Monocle3) and the Cell Surface Protein Atlas, we profiled surface proteins for each cluster at Day 0 and identified a set of unique surface markers (SLC3A, LYPD3, TACSTD2, DSC2) from undifferentiated basal cells that express both basal (TP63+, K14+) and luminal markers (K8+, K18+), potentially serving as a bi-potent prostate epithelial cells. Conclusion: Our data have identified unique populations present in our prostate differentiation model expressing both luminal and basal signatures which can be isolated using identified surface markers to investigate the role of bi-potent cells in prostate differentiation and oncogenesis. Citation Format: Hunain Khawaja, Cynthia Miranti. Identifying the molecular signature of bi-potent prostate epithelial cells through scRNA-seq [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B006.