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    Single-cell analysis identifies LY6D as a marker linking castration-resistant prostate luminal cells to prostate progenitors and cancer

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    Authors
    Barros-Silva, Joao D
    Linn, D
    Steiner, I
    Guo, G
    Ali, Adnan
    Pakula, H
    Ashton, Garry
    Peset, I
    Brown, Michael D
    Clarke, Noel W
    Bronson, R
    Yuan, G
    Orkin, S
    Li, Z
    Baena, Esther
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    Affiliation
    Prostate Oncobiology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, UK
    Issue Date
    2018
    
    Metadata
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    Abstract
    The exact identity of castrate-resistant (CR) cells and their relation to CR prostate cancer (CRPC) is unresolved. We use single-cell gene profiling to analyze the molecular heterogeneity in basal and luminal compartments. Within the luminal compartment, we identify a subset of cells intrinsically resistant to castration with a bi-lineage gene expression pattern. We discover LY6D as a marker of CR prostate progenitors with multipotent differentiation and enriched organoid-forming capacity. Lineage tracing further reveals that LY6D+ CR luminal cells can produce LY6D- luminal cells. In contrast, in luminal cells lacking PTEN, LY6D+ cells predominantly give rise to LY6D+ tumor cells, contributing to high-grade PIN lesions. Gene expression analyses in patients' biopsies indicate that LY6D expression correlates with early disease progression, including progression to CRPC. Our studies thus identify a subpopulation of luminal progenitors characterized by LY6D expression and intrinsic castration resistance. LY6D may serve as a prognostic maker for advanced prostate cancer.
    Citation
    Barros-Silva JD, Linn DE, Steiner I, Guo G, Ali A, Pakula H, et al. Single-cell analysis identifies LY6D as a marker linking castration-resistant prostate luminal cells to prostate progenitors and cancer. Cell Rep. 2018 Dec 18;25(12):3504-18 e6.
    Journal
    Cell Reports
    URI
    http://hdl.handle.net/10541/621503
    DOI
    10.1016/j.celrep.2018.11.069
    PubMed ID
    30566873
    Additional Links
    https://dx.doi.org/10.1016/j.celrep.2018.11.069
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.celrep.2018.11.069
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