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

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Renaud Mevel
  • Ivana Steiner
  • Susan Mason
  • Laura C. A. Galbraith
  • Rahima Patel
  • Muhammad Fadlullah Wilmot
  • Imran Ahmad
  • Hing Leung
  • Pedro Oliveira
  • Karen Blyth
  • Esther Baena

Abstract

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.

Bibliographical metadata

Original languageEnglish
JournaleLife
Publication statusAccepted/In press - 7 Oct 2020