First Author | Mevel R | Year | 2020 |
Journal | Elife | Volume | 9 |
PubMed ID | 33025905 | Mgi Jnum | J:298674 |
Mgi Id | MGI:6477092 | Doi | 10.7554/eLife.60225 |
Citation | Mevel R, et al. (2020) RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development. Elife 9:e60225 |
abstractText | 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. |