RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development

• Main Authors: Renaud Mevel, Ivana Steiner, Susan Mason, Laura CA Galbraith, Rahima Patel, Muhammad ZH Fadlullah, Imran Ahmad, Hing Y Leung, Pedro Oliveira, Karen Blyth, Esther Baena, Georges Lacaud
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2020-10-01
• Series: eLife
• Subjects: RUNX1; prostate; development; proximal luminal cells; intrinsic castration-resistance; single-cell RNA-seq
• Online Access: https://elifesciences.org/articles/60225

The characterization of prostate epithelial hierarchy and lineage heterogeneity is critical to understand its regenerative properties and malignancies. Here, we report that the transcription factor RUNX1 marks a specific subpopulation of proximal luminal cells (PLCs), enriched in the periurethral region of the developing and adult mouse prostate, and distinct from the previously identified NKX3.1+ luminal castration-resistant cells. Using scRNA-seq profiling and genetic lineage tracing, we show that RUNX1+ PLCs are unaffected by androgen deprivation, and do not contribute to the regeneration of the distal luminal compartments. Furthermore, we demonstrate that a transcriptionally similar RUNX1+ population emerges at the onset of embryonic prostate specification to populate the proximal region of the ducts. Collectively, our results reveal that RUNX1+ PLCs is an intrinsic castration-resistant and self-sustained lineage that emerges early during prostate development and provide new insights into the lineage relationships of the prostate epithelium.