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SRP115904
Homo sapiens
36 Downloadable Samples
Illumina HiSeq 2500
Description
We discovered a rare missense mutation in NR1H4 (R436H), which encodes the farnesoid X receptor (FXR), associating with lower levels of total cholesterol in the Icelandic population. To explore the effects of R436H we used CRISPR-Cas9 to generate homozygous NR1H4 R436H and NR1H4 knockout human iPSC lines which we differentiated to hepatocytes. Hepatocytes were treated with an FXR agonist for 24 hours and transcript abundance measured by RNA-seq. The global response to FXR activation in NR1H4 R436H cells was very similar to that of wild-type cells showing that it is not a loss-of-function mutation. However, we did observe subtle gene expression differences compatible with an effect on lipids when we compared R436H agonist treated hepatocytes to wild-type agonist treated hepatocytes. Overall design: RNA-seq was performed on wild-type, NR1H4 knockout and NR1H4 R436H iPSC-derived hepatocytes treated with FXR agonist GW4064.
Publication Title
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus, Homo sapiens
- 9 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Epigenetic regulation is based upon a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets to treat a range of diseases including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach to control infection, persistence, and the resulting recurrent disease. The histone methyltransferases EZH2 and EZH1 (EZH2/1) are epigenetic repressors that suppress gene transcription via propagation of repressive H3K27me3 enriched chromatin domains. However, while EZH2/1 are implicated in repression of herpesviral gene expression, inhibitors of these enzymes suppressed HSV primary infection in vitro and in vivo. Furthermore, these compounds blocked lytic viral replication following induction of HSV reactivation in latently infected sensory ganglia. Suppression correlated with the induction of multiple inflammatory, stress, and anti-pathogen pathways as well as enhanced recruitment of immune cells to in vivo infection sites. Importantly, EZH2/1 inhibitors induced a cellular antiviral state that also suppressed infection with DNA (hCMV, Adenovirus) and RNA (Zika virus) viruses. Thus, EZH2/1 inhibitors have considerable potential as general antivirals through activation of cellular antiviral and immune responses.
Publication Title
Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We used microarrays to investigate the transcriptome of 6 days old male flies exposed to either 15 or 25 C development at either constant or fluctuating temperatures. Further, we investigated gene expression at benign (20C) and high (35C) temperatures
Publication Title
Thermal fluctuations affect the transcriptome through mechanisms independent of average temperature.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Resveratrol treatment has shown beneficial effects on experimental models of non-alcoholic liver disease (NAFLD). In this pilot-size, clinical trial we teated the therapeutic potential in NAFLD patients.
Publication Title
Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 166 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
The present work aimed to identify reference genes for RT-qPCR studies of hypoxia in cervical cancer. From 422 candidate reference genes selected from the literature, we used Illumina array-based expression profiles to identify 182 genes not affected by hypoxia treatment in eight cervical cancer cell lines or correlated with the hypoxia-associated dynamic contrast-enhanced magnetic resonance imaging parameter ABrix in 42 patients. Among these genes, we selected nine candidates (CHCHD1, GNB2L1, IPO8, LASP1, RPL27A, RPS12, SOD1, SRSF9, TMBIM6) that were not associated with tumor volume, stage, lymph node involvement or disease progression in array data of 150 patients, for further testing by RT-qPCR. geNorm and NormFinder analyses of RT-qPCR data of 74 patients identified CHCHD1, SRSF9 and TMBIM6 as the most suitable set of reference genes, with stable expression both overall and across patient subgroups with different hypoxia status (ABrix) and clinical parameters. The suitability of the three candidates as reference genes were validated in studies of the hypoxia-induced genes DDIT3, ERO1A, and STC2. After normalizing with CHCHD1, SRSF9 and TMBIM6, the RT-qPCR data of these genes showed a significant correlation with Illumina expression (P<0.001, n=74) and ABrix (P<0.05, n=32), and the STC2 data were associated with clinical outcome, in accordance with the Illumina data. Thus, CHCHD1, SRSF9 and TMBIM6 seem to be suitable reference genes for studying hypoxia-related gene expression in cervical cancer samples by RT-qPCR. STC2 might be a useful prognostic hypoxia biomarker in cervical cancer that warrants further investigation.
Publication Title
Identification and Validation of Reference Genes for RT-qPCR Studies of Hypoxia in Squamous Cervical Cancer Patients.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Aim of the study was to characterize the transcriptional response of human primary renal proximal tubule epithelial cells (RPTEC) to low oxygen stress.
Publication Title
The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used microarrays to assess gene expression profiling of 6 patients with a mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene (INSR) and 10 matched healthy controls
Publication Title
A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance.
Sample Metadata Fields
Specimen part
View Samples- Schizosaccharomyces pombe
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The response to nitrogen starvation was studied in S. pombe. This experiment contains expression data from Affymetrix Yeast 2.0 arrays.
Publication Title
Nitrogen depletion in the fission yeast Schizosaccharomyces pombe causes nucleosome loss in both promoters and coding regions of activated genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 80 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Emerging biomarkers based on medical images and molecular characterization of tumor biopsies open up for combining the two disciplines and exploiting their synergy in treatment planning. We compared pretreatment classification of cervical cancer patients by two previously validated imaging- and gene-based hypoxia biomarkers, evaluated the influence of intratumor heterogeneity, and investigated the benefit of combining them in prediction of treatment failure. The imaging-based biomarker was hypoxic fraction, determined from diagnostic dynamic contrast enhanced (DCE)-MR images. The gene-based biomarker was a hypoxia gene expression signature determined from tumor biopsies. Paired data were available for 118 patients. Intratumor heterogeneity was assessed by variance analysis of MR images and multiple biopsies from the same tumor. The two biomarkers were combined using a dimension-reduction procedure. The biomarkers classified 75% of the tumors with the same hypoxia status. Both intratumor heterogeneity and distribution pattern of hypoxia from imaging were unrelated to inconsistent classification by the two biomarkers, and the hypoxia status of the slice covering the biopsy region was representative of the whole tumor. Hypoxia by genes was independent on tumor cell fraction and showed minor heterogeneity across multiple biopsies in 9 tumors. This suggested that the two biomarkers could contain complementary biological information. Combination of the biomarkers into a composite score led to improved prediction of treatment failure (HR:7.3) compared to imaging (HR:3.8) and genes (HR:3.0) and prognostic impact in multivariate analysis with clinical variables. In conclusion, combining imaging- and gene-based biomarkers enables more precise and informative assessment of hypoxia-related treatment resistance in cervical cancer, independent of intratumor heterogeneity.
Publication Title
Combining imaging- and gene-based hypoxia biomarkers in cervical cancer improves prediction of chemoradiotherapy failure independent of intratumour heterogeneity.
Sample Metadata Fields
Specimen part
View Samples