Dataset Information

Expression data and H3K27me3 occupancy profiling by high throughput sequencing from control and SETD2 knockout organoids cells.

ABSTRACT: To understand the molecular basis how Setd2 loss enhances metastatic traits of PCa, we carried out RNA-seq and H3k27me3 Chip-seq using mice-derived prostatic organoid cells from 3-month-old PtenPC+/− and PtenPC+/−;Setd2PC−/− mice.To further validate Setd2 loss accelerated prostate tumorigenesis is dependent on EZH2 upregulation,we conduct high throughput sequencing of organoid cells derived from PtenPC+/− and PtenPC+/−;Setd2PC−/− mice with Ezh2 knockout.To understand the molecular basis whether the tumor suppressive function of Setd2 is depends on its methylation of EZH2 at k735, we also carried out RNA-seq using mice-derived prostatic organoid cells from 2-month-old PtenPC-/- and PtenPC-/-;Ezh2K735R mice.We integrated all the RNA-seq and chip-seq data generated from organoid cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE136830 | GEO | 2020/12/22

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Castration-resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen-deprivation remain poorly described despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild type mouse prostates a rare population of luminal progenitor cells that we called LSCmed according to their FACS profile (Lin?/Sca-1+/CD49fmed). Here we investigated the prevalence and castration resistance of LSCmed in various mouse models of prostate tumorigenesis. In intact mice, we show that LSCmed prevalence remains low (5-10% of epithelial cells) when prostatic androgen receptor signaling unaltered (malignant Hi-Myc mice) but significantly increases in models exhibiting reduced prostatic androgen receptor signaling, rising up to 30% in premalignant tumors (Pb-PRL mice) and to >80% in castration-resistant prostate tumors driven by Pten loss (Ptenpc-/- mice). LSCmed tolerance to androgen deprivation was demonstrated by their persistence (Ptenpc-/-) or further enrichment (Pb-PRL) 2-3 weeks after castration as evidenced by FACS analysis. Transcriptomic analysis revealed that LSCmed represent a unique cell entity as their gene-expression profile is different from luminal and basal/stem cells, but shares markers of each. Their intrinsic androgen signaling is markedly decreased, which explains why LSCmed tolerate androgen-deprivation. This also enlightens why Ptenpc-/- tumors are castration-resistant since LSCmed represent the most prevalent cell type in this model. We validated CK4 as a specific marker for LSCmed on sorted cells and prostate tissues by immunostaining, allowing for the detection of LSCmed in various mouse prostate specimens. In castrated Ptenpc-/- prostates, BrdU staining revealed massive proliferation of CK4+ cells, further demonstrating their key role in castration-resistant prostate cancer progression. In all, this study identifies LSCmed as a probable source of prostate cancer relapse after androgen deprivation and as a new therapeutic target for the prevention of castrate-resistant prostate cancer.

Dataset Information

Expression data and H3K27me3 occupancy profiling by high throughput sequencing from control and SETD2 knockout organoids cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure