Transcriptomics,Genomics

Dataset Information

149

Developing a Novel Two-Dimensional Culture System to Enrich Human Prostate Luminal Progenitors That Can Function as a Cell of Origin for Prostate Cancer


ABSTRACT: Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulkNHPluminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human mammary epithelial progenitor cells, when combined with the ROCK inhibitor, can readily propagate a population of progenitor-like cells from the primary NHP luminal cell isolates. Such functionally defined luminal progenitors can be transformed by distinct sets of genetic perturbations (i.e., AR+AKT/ERG or c-MYC+PTEN knockout) to form tumor glands. Genome-wide RNA-Seq analysis of freshly purified unperturbed human benign prostatic basal and luminal cells and culture-expanded lineage specific stem/progenitor populations reveals that the luminal progenitors possess a distinct gene expression profile that is greatly enriched in advanced, castration-resistant, and metastatic PCa, and it associates with poor patient survival. The ability of the simple two-dimensional culture system reported herein to greatly enrichNHPprogenitor-like cells should facilitate biological and biochemical studies as well as high-throughput screening in these cells and in progenitor-like PCa cells. Overall design: Human total RNA profiles of HPCa167N benign prostatic bulk epithelial cells and freshly purified basal and luminal populations cultured primarily in WIT and PrEGM media by deep RNA-seq.

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Dingxiao Zhang  

PROVIDER: GSE74698 | GEO | 2016-09-25

SECONDARY ACCESSION(S): PRJNA301175

REPOSITORIES: GEO

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Publications

Developing a Novel Two-Dimensional Culture System to Enrich Human Prostate Luminal Progenitors that Can Function as a Cell of Origin for Prostate Cancer.

Zhang Dingxiao D   Lin Kevin K   Lu Yue Y   Rycaj Kiera K   Zhong Yi Y   Chao Hsueh-Ping HP   Calhoun-Davis Tammy T   Shen Jianjun J   Tang Dean G DG  

Stem cells translational medicine 20160929 3


Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulk NHP luminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human  ...[more]

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