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accession-icon GSE22606
Identification of an SRF- and androgen-dependent gene signature in prostate cancer
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The androgen receptor (AR) is the principal target for treatment of non-organ confined prostate cancer (PCa). Systems and bioinformatics approaches suggest that considerable variation exists in the mechanisms by which AR regulates expression of effector genes and point towards a role for secondary transcription factors (TFs) therein. We identified a novel indirect mechanism of androgen action in which effects of androgens on PCa cells are mediated by Serum Response Factor (SRF). To identify and characterize genes and cellular processes that are androgen-regulated in an SRF-dependent manner in PCa, Affymetrix HG-U133 Plus 2.0 GeneChip Array analysis was performed starting from RNA obtained from LNCaP cells in which androgen stimulation was combined with siRNA-mediated SRF silencing. To this end, LNCaP cells were seeded in 60 mm dishes at a density of 550,000 cells per dish in antibiotic-free medium. The next day, cells were transfected with siGenome SmartPool siRNA targeting SRF (Dharmacon, Lafayette, CO) or a custom-made control SmartPool targeting luciferase (LUC condition) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA) following the manufacturers instructions. Forty-two hours after transfection, cells were treated with 5nM R1881 or ethanol vehicle. 3 biological triplicates were included per treatment group. Forty-eight hours later, cells were harvested in Trizol reagent (Invitrogen). RNA was isolated, purified on RNeasy columns (Qiagen, Germantown, MD) and checked for integrity by Agilent testing (Affymetrix, Santa Clara, CA). cDNA was generated and hybridized to Human Genome U133 Plus 2.0 arrays (Affymetrix) according to the manufacturers instructions at the Mayo Clinic Advanced Genomics Technology Microarray Shared Resource core facility.

Publication Title

Identification of a clinically relevant androgen-dependent gene signature in prostate cancer.

Sample Metadata Fields

Cell line

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accession-icon SRP066238
Lipid degradation promotes prostate cancer cell survival
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p=0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. Overall design: Two biological replicates for prostate cancer cell line (LNCaP) and cell line representing normal prostate epithelium (RWPE-1), transfected with scrambled siRNA or two different siRNAs targeting ECI2. RNA was extracted and used for RNA-sequencing. The processed files provided are compressed folders containing multiple output files from CuffDiff runs estimating differentially expressed transcripts between the indicated ECI2 siRNA treated cells versus cells treated with Scrambled siRNAs.

Publication Title

Lipid degradation promotes prostate cancer cell survival.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE49039
Comparison of gene expression from thymocyte populations and equivalent OP9-DL1 cultured cells
  • organism-icon Homo sapiens
  • sample-icon 1 Downloadable Sample
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

Comparison between ex vivo immature, mature and stimulated T cells and in vitro generated counterparts. The T cells generated in vitro were cultured on OP9-DL1 stroma supplied with growth factors.

Publication Title

In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.

Sample Metadata Fields

Specimen part

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accession-icon GSE10362
Expression data from sequential P. aeruginosa cystic fibrosis (CF) isolates
  • organism-icon Pseudomonas aeruginosa
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Pseudomonas aeruginosa Array (paeg1a)

Description

To provide a more detailed survey of adaptive changes in the physiology of P. aeruginosa (PA) during long-term infection of the cystic fibrosis (CF) lung, we performed a comparative proteome and transcriptome analysis of a set of isogenic sequential non-mutator and mutator isolates from three selected CF patients. Recently, we showed that during CF lung persistence PA mutators converge to a virulence-attenuated phenotype. In this study, we demonstrate that besides virulence-associated traits (VATs) the adaptation process of PA predominantly comprises metabolic pathways. In end-stage mutator strains, transcripts of genes encoding VATs, chemotaxis, degradation of aromatic compounds and several two-component regulatory systems were decreased. In contrast, several transcripts of genes or proteins involved in metabolism of fatty acids, nucleotides, amino acids and the generation of energy were increased. Of particular interest is the increased expression level of genes involved in (i) the anaerobic arginine-deiminase pathway, (ii) the anaerobic respiration such as nitrate-uptake protein OprF, redox-active azurin and cytchrome c551 peroxidase, (iii) the micro-aerobic respiration such as high oxygen-affinity cytochrome oxidase cbb3 (iv) the tricarboxylic acid cycle (TCA), glyoxylate shunt and anaplerotic carboxylation reactions to oxaloacetate. Strikingly, an increased transcription of the anaerobic regulator gene anr correlates with the up-regulation of ANR-dependent genes. In conclusion, these changes in transcriptome and proteome indicate an adaptive shift towards constitutive expression of genes of metabolic pathways obviously required for growth under micro-aerobic and nutritional conditions of suppurative CF lung tissue. Finally, these results provide us with new targets for antimicrobial agents and biomarkers reflecting adaptation of PA towards progressive CF lung disease.

Publication Title

Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE147231
Identification of human cytotoxic ILC3s
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Clariom S Pico Assay HT (clariomshumanht)

Description

Human ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.

Publication Title

Identification of human cytotoxic ILC3s.

Sample Metadata Fields

Specimen part, Subject

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accession-icon SRP070694
BASP1 modifies the Tamoxifen response
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2500

Description

We report that WT1 transcriptional repressor protein BASP1 interacts with oestrogen receptor alpha (Era), and interaction which in enhanced in the presence of Tamoxifen. We utilised RNASeq to identify common BASP1 and ERa target genes as well as Tamoxifen responsive genes that are altered in the absence of BASP1. Overall design: Total mRNA sequencing analysis of MCF7 cells treated with either siRNA against BASP1 or negative control siRNA, with and without Tamoxifen treatment. Each experiment was performed in triplicate.

Publication Title

BASP1 interacts with oestrogen receptor α and modifies the tamoxifen response.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP040269
mRNA profile in DR-related mutants
  • organism-icon Caenorhabditis elegans
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Dietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the Caenorhabditis elegans HNF4a-related nuclear hormone receptor NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. nhr-62 mediates the longevity of eat-2 mutants, a genetic mimetic of dietary restriction, and blunts the longevity response of DR induced by bacterial food dilution at low nutrient levels. Metabolic changes associated with DR, including decreased Oil Red O staining, decreased triglyceride levels, and increased autophagy are partly reversed by mutation of nhr-62. Additionally, the DR fatty acid profile is altered in nhr-62mutants. Expression profiles reveal that several hundred genes induced by DR depend on the activity of NHR-62, including a putative lipase required for the DR response. This study provides critical evidence of nuclear hormone receptor regulation of the DR longevity response, suggesting hormonal and metabolic control of life span. Overall design: Young adult worms before bearing eggs inside were collected. N2 serves as the control of wild type. 3 biological replicates included in this experiment.

Publication Title

Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans.

Sample Metadata Fields

Subject

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accession-icon SRP045900
Next Generation Sequencing of Pattern II Demyelinating Brain Lesions from a Multiple Sclerosis Patient
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination. Overall design: Examination of 3 different demyelinating lesions identified by Immunohistopathology.

Publication Title

Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE110087
Gene expression profiles of primary samples of acute myeloid leukemia (AML)
  • organism-icon Homo sapiens
  • sample-icon 41 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

As part of a clinical trial of the MDM2 inhibitor DS-3032b, 41 primary tumor samples were obtained before treatment from 38 patients newly diagnosed with AML, or relapsed or refractory to standard induction chemotherapy

Publication Title

Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition.

Sample Metadata Fields

Specimen part, Disease, Disease stage

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accession-icon GSE46546
Expression data from FACS purified nociceptor neurons from peripheral sensory ganglia
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

The goal of this study was to analyze global gene expression in specific populations of nociceptor sensory neurons, the neurons that detect damaging/noxious stimuli.

Publication Title

Bacteria activate sensory neurons that modulate pain and inflammation.

Sample Metadata Fields

Specimen part

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...

refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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