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Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation.


ABSTRACT: Identification of defined cell populations with stem/progenitor properties is key for understanding prostate development and tumorigenesis. Here we show that the polycomb repressor protein Bmi1 marks a population of castration-resistant luminal epithelial cells enriched in the mouse proximal prostate. We employ lineage tracing to show that these castration-resistant Bmi1-expressing cells (or CARBs) are capable of tissue regeneration and self-renewal. Notably, CARBs are distinct from the previously described luminal castration-resistant Nkx3.1-expressing cells (CARNs). CARBs can serve as a prostate cancer cell-of-origin upon Pten deletion, yielding luminal prostate tumours. Clonal analysis using the R26R-confetti allele indicates preferential tumour initiation from CARBs localized to the proximal prostate. These studies identify Bmi1 as a marker for a distinct population of castration-resistant luminal epithelial cells enriched in the proximal prostate that can serve as a cell of origin for prostate cancer.

SUBMITTER: Yoo YA 

PROVIDER: S-EPMC5059479 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation.

Yoo Young A YA   Roh Meejeon M   Naseem Anum F AF   Lysy Barbara B   Desouki Mohamed M MM   Unno Kenji K   Abdulkadir Sarki A SA  

Nature communications 20161005


Identification of defined cell populations with stem/progenitor properties is key for understanding prostate development and tumorigenesis. Here we show that the polycomb repressor protein Bmi1 marks a population of castration-resistant luminal epithelial cells enriched in the mouse proximal prostate. We employ lineage tracing to show that these castration-resistant Bmi1-expressing cells (or CARBs) are capable of tissue regeneration and self-renewal. Notably, CARBs are distinct from the previous  ...[more]

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2020-10-07 | GSE151944 | GEO