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Accession IconGSE92473

Microarray expression profiling data for sorted prostate epithelial subpopulations based on LY6D

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

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Description
In the normal prostate, most basal and some luminal cells are castration-resistant (CR). The identity of these CR cells and their relation to CR prostate cancer are unresolved. We compared single-cell expression profiles of prostate cells sorted from hormonally nave (HN) and castrated mice. We found both basal and luminal-localized cells, particularly the latter, were molecularly heterogeneous. CR luminal cells and a subset of HN luminal cells exhibited a similar intermediate expression pattern, including high-level expression of multiple prostate stem/progenitor marker genes and androgen receptor gene. We validated LY6D as a marker linking CR luminal cells to luminal progenitors. LY6D+ prostate cells, including LY6D+ luminal cells, were enriched for organoid-forming potential regardless of the presence or absence of androgen. Krt8-based lineage-tracing revealed that LY6D+ CR luminal cells produced LY6D- normal luminal cells upon regeneration, but LY6D+ luminal cancer cells under PTEN-deficiency. Furthermore, prostate cancers originating from CR luminal cells (LY6D+) exhibited a more advanced phenotype than those from HN luminal cells (LY6D+ or LY6D-). Lastly, LY6D amplification/upregulation appear associated with advanced prostate cancer in patient samples. Together, our studies demonstrate LY6D as a novel progenitor marker predictive of lethal CR disease.
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