Acquired stemness by luminal cells

Rare cell types in the prostate are reported to have stem cell properties based on organ regeneration potential following castration. Here, we use single cell RNA-seq (scRNA-Seq) to characterize these populations from the murine and human prostate in hormonally intact and androgen deprived conditions. Prostate cells from hormonally intact mice partitioned into one large subset of basal epithelial cells, another large subset of luminal epithelial cells, which we designate luminal 1 and two rare luminal populations: luminal 2 and luminal 3. Luminal cells that persist following castration display enhanced organoid regeneration potential, particularly within 1-2 days of androgen addback, and contribute equipotently to prostatic regeneration as revealed by lineage tracing. This regeneration is mediated, in part, through the orchestrated expression of Nrg2, Igf1, Fgf10 and Rspo3 by distinct populations of androgen-responsive mesenchymal and smooth muscle cells. Thus, luminal cells that persist post-castration undergo a cell state change that primes a proliferative response to microenvironment signals, analogous to other models of tissue injury such as liver damage. Citation Format: Wouter Karthaus, Matan Hofree, Danielle Choi, Eliot L. Linton, Mesruh Turkekul, Alborz Bejnood, Brett Carver, Anuhandra Gopalan, Vincent Laudone, Moshe Biton, Ojasvi Chaudhary, Ignas Masilionis, Linas Mazutis, Dana Pe9er, Aviv Regev, Charles Sawyers. Acquired stemness by luminal cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5722.