Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration

Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Dingxiao Zhang, Collene Jeter, Shuai Gong, Amanda Tracz, Yue Lu, Jianjun Shen, Dean G. Tang The existence of slow-cycling luminal cells in the prostate has been suggested, but their identity and functional properties remain unknown. Using a bigenic mouse model to earmark, isolate, and characterize the quiescent stem-like cells, we identify a label-retaining cell (LRC) population in the luminal cell layer as luminal progenitors. Molecular and biological characterizations show that these luminal LRCs are significantly enriched in the mouse proximal prostate, exhibit relative dormancy, display bipotency in both in vitro and in vivo assays, and express a stem/progenitor gene signature with resemblance to aggressive prostate cancer. Importantly, these LRCs, compared with bulk luminal cells, maintain a lower level of androgen receptor (AR) expression and are less androgen dependent and also castration resistant in vivo. Finally, analysis of phenotypic markers reveals heterogeneity within the luminal progenitor cell pool. Our study establishes luminal LRCs as progenitors that may serve as a cellular origin for castration-resistant prostate cancer. Graphical abstract Teaser In this article, Tang and colleagues, by using an unbiased bigenic mouse model to specifically earmark, prospectively isolate, and functionally characterize the quiescent stem-like cells, report a label-retaining ce...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research