The Androgen Receptor (AR) is the key-driving transcription factor in prostate cancer, tightly controlled by epigenetic regulation. To date, most epigenetic profiling has been performed in cell lines or limited tissue samples. To comprehensively study the epigenetic landscape, we complemented RNA-seq with ChIP-seq for AR and histone modification marks (H3K27ac, H3K4me3, H3K27me3) in 100 primary prostate carcinomas. Integrative molecular subtyping of the five data streams revealed three major subtypes of which two were clearly TMPRSS2-ERG dictated. Importantly, a third novel subtype was identified, with low AR chromatin binding and activity, even though the receptor was clearly expressed. While positive for neuroendocrine-hallmark genes, these tumors were copy number-neutral with low mutation burden, significantly depleted for genes characteristic of poor-outcome associated luminal B-subtype. We present a rich novel resource on transcriptional and epigenetic control in prostate cancer, revealing a tight control of gene regulation differentially dictated by AR over the three subtypes. Overall design: RNA-seq data for primary prostate carcinomas
Integrative epigenetic taxonomy of primary prostate cancer.
Specimen part, Subject
View SamplesWe compared transcriptional profiles of CD4+ and CD8+ T lymphocytes from HIV infected individuals before and 1 year after interruption of antiretroviral therapy (ART).
Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.
Sex, Age, Specimen part, Disease stage, Race, Subject
View SamplesCancer-associated inflammatory processes in the tumour microenvironment, as well as systemically, are strongly linked with poor disease outcome in cancer patients. For most human solid tumour types, high systemic neutrophil-to-lymphocyte ratios (NLR) are associated with increased metastasis and poor overall survival and recent experimental studies have demonstrated a causal relationship between neutrophils and metastasis formation. However, to date, the cancer cell-intrinsic mechanisms dictating the substantial heterogeneity in systemic neutrophilic inflammation between tumour-bearing hosts are largely unresolved. Using a panel of 16 distinct genetically engineered mouse models (GEMMs) for breast cancer, we demonstrate that tumour cell-intrinsic loss of p53 changes the phenotype and function of macrophages in the microenvironment, leading to activation of a systemic inflammatory cascade that drives neutrophil expansion. Mechanistically, p53 loss in cancer cells induces secretion of Wnt ligands that act in a paracrine fashion to stimulate IL-1b production from tumour-associated macrophages. Intratumoural IL-1ß production stimulates an inflammatory cascade leading to the systemic accumulation of neutrophils. Pharmacological and genetic blockade of cancer cell-derived Wnt secretion reverses IL-1ß expression by macrophages and subsequent systemic neutrophilic inflammation. Collectively, using pre-clinical mouse models for breast cancer, we demonstrate a novel mechanistic link between loss of p53 in cancer cells, Wnt ligand secretion and systemic immune activation. This illustrates the importance of cancer cell-intrinsic genetic aberrations in dictating cancer-associated inflammation. These insights set the stage for personalized immune intervention strategies for cancer patients. Overall design: In this study, gene expression profiles of tumours from genetically engineered mouse models (GEMMs) were analysed using RNA sequencing. Analysis was performed on bulk tumours of 10 GEMMs with different tissue-specific mutations driving tumorigenesis, totalling to 125 different tumours (n=5 or more per group). Subsequently, samples were grouped according to p53 status of the tumour (models containing Trp53 floxed alleles, or not) and comparisons were made between p53-KO and p53-WT tumours.
Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis.
Cell line, Subject
View SamplesIslets are known to respond to changes in ambient glucose. To quantify the transcriptome-wide changes in ambient glucose, we compared transcriptome of islets exposed to low and high glucose. Overall design: Isolated islets from wild type male mice. Islets from adult males were pooled, cultured overnight in RPMI containing 11 mM glucose. The next day, all islets were starved in RPMI containing 2.8 mM glucose for 2 hours before stimulation with 2.8 mM glucose or 16.8 mM glucose for 12 hours. Islets were lysed in Trizol for RNA isolation and library construction.
The transcriptional landscape of mouse beta cells compared to human beta cells reveals notable species differences in long non-coding RNA and protein-coding gene expression.
No sample metadata fields
View SamplesRodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology. We generated comprehensive transcriptomes of mouse delta, beta and alpha cells using two separate triple transgenic mouse models generated for this purpose. This enables systematic comparison across thousands of genes between the three major endocrine cell types of the islets of Langerhans whose principal hormones control nutrient homeostasis. Overall design: FACS purified delta or alpha cells and beta cells from the same islets. Islets were isolated from triple transgenic offspring of a cross between mIns1-H2b-mCherry (Jax # 028589) and either Sst-Cre (delta) or Gcg-cre (alpha) cells and a floxed YFP allele to label delta or alpha cells, respectively. Islets from replicate groups of 10 to 12 triple transgenic animals for each group were pooled by sex to obtain sufficient material. Pooled islets were dissociated, sorted and collect in Trizol for RNA isolation and library construction.
Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets.
Sex, Specimen part, Subject
View SamplesThe identification of HCC patients with different risks of recurrence by incorporating the status of clinicopathological features available at diagnosis and gene expression profiling associated with recurrence
Identification and validation of a novel gene signature associated with the recurrence of human hepatocellular carcinoma.
None
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sex
View SamplesThe second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected, rank-order gene expression, and functional genomic analysis.
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sex
View SamplesThe objective of this study was to identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants.
Global gene expression analysis of term amniotic fluid cell-free fetal RNA.
Sex
View SamplesThe objective of this study was to identify the tissue expression patterns and biological pathways enriched in term cord blood fetal RNA of obese women compared to lean
Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case-control study.
Specimen part
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