The Contribution of Sox2+ Cells to Prostate Epithelium Development, Regeneration, and Hyperplasia

Despite intensive study, gaps remain in our understanding of prostate epithelial stem cell specification and resulting lineage relationships. Identification of defined epithelial cell populations with progenitor properties is critical for understanding prostatic development and disease. Here we show that the stem cell transcription factor Sox2 marks a population of castration-resistant basal and luminal cells. We utilize lineage tracing to demonstrate that the Sox2 lineage is capable of self-renewal and contributes to prostatic regeneration. Notably, Sox2 is expressed in persisting cells in response to castration. Sox2 ChIP-seq analysis in prostate human epithelial cells demonstrates Sox2 binding and potential regulation of both stem and non-stem cell associated Sox2 targets when compared to human embryonic stem cells. Taken together, these data implicate Sox2 as a marker and potential regulatory factor of the adult progenitor cell compartment in the prostate. Further, we examine a novel mouse model of bladder outlet obstruction using longitudinal magnetic resonance imaging (MRI) and histologic analyses to quantify changes in prostatic volume, urethral volume, and genitourinary vascularization over time. Our data demonstrate significant prostatic enlargement by 12 weeks post-treatment, with no detectable immune infiltrate by macrophages, T- or B-cell populations. Importantly, the percentage of cell death as measured by TUNEL was significantly decreased in the prostatic epithelium of treated animals as compared to controls. We found no significant change in prostate cell proliferation in treated mice when compared to controls. Additionally, we observed no significant changes in Sox2 expression in human samples of benign prostatic hyperplasia nodules as compared to adjacent normal epithelial tissues.