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GSE136801
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Primary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. Mutations in different genes increase aldosterone production in PA, but additional mechanisms may contribute to increased cell proliferation and aldosterone producing adenoma (APA) development. We performed transcriptome analysis in APA and identified retinoic acid receptor alpha (RARα) signaling as a central molecular network involved in nodule formation. To understand how RARα modulates adrenal structure and function, we explored the adrenal phenotype of male and female Rarα knockout mice. Inactivation of Rarα in mice led to major structural disorganization of the adrenal cortex in both sexes, with increased adrenal cortex size in female mice and increased cell proliferation in males. Abnormalities of vessel architecture and extracellular matrix were due to decreased Vegfa expression and modifications in extracellular matrix components. On the molecular level, Rarα inactivation leads to inhibition of non-canonical Wnt signaling, without affecting the canonical Wnt pathway nor PKA signaling. Our study suggests that Rarα contributes to the maintenance of normal adrenal cortex structure and cell proliferation, by modulating Wnt signaling. Dysregulation of this interaction may contribute to abnormal cell proliferation, creating a propitious environment for the emergence of specific driver mutations in PA.
Publication Title
Retinoic acid receptor α as a novel contributor to adrenal cortex structure and function through interactions with Wnt and Vegfa signalling.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens, Rattus norvegicus
- 34 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Significant qualitative and quantitative differences exist between humans and the animal models used in research. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this difference using a cross-species methodology by investigating species specific differences of the peroxisome proliferator activator receptor (PPAR) alpha in rat and human.
Publication Title
Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Significant qualitative and quantitative differences exist between humans and the animal models used in research. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this difference using a cross-species methodology by investigating species specific differences of the peroxisome proliferator activator receptor (PPAR) alpha in rat and human.
Publication Title
Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Leptin binding to the leptin receptor (LepR) causes rapid signaling to the nucleus. We investigated the early (2 hr) transcriptional response to acute leptin injectio (intracerebroventricular)
Publication Title
Ancient origins and evolutionary conservation of intracellular and neural signaling pathways engaged by the leptin receptor.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice are all more sensitive than wild type (WT) mice to dextran sulfate sodium (DSS)-induced colitis. The purpose of this study was to determine which genes are differentially induced by DSS treatment in the colon of Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice compared to WT mice. The results demonstrate higher induction of proinflammatory gene expression in Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice than in WT mice after DSS treatment. The majority of genes whose expression is increased in Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice but not in WT mice are interferon-inducible genes. Thus, Peptidoglycan Recognition Proteins Pglyrp1, Pglyrp2, Pglyrp3, and Pglyrp4 protect mice from excessive inflammatory response and damage to the colon by limiting expression of interferon-inducible genes in the colon.
Publication Title
Peptidoglycan recognition proteins protect mice from experimental colitis by promoting normal gut flora and preventing induction of interferon-gamma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 49 Downloadable Samples
Illumina HiSeq 2500, NextSeq 500
Description
Purpose: the goal of this study was to test whether the amounts of genome-encoded Line-1s are influenced by TUTases and Mov10 Methods: RNA-Seq data were obtained for PA-1 or Hek293 Flp-IN T-Rex cells in which wild-type or mutant TUTases or Mov10 were overexpressed or the proteins were depleted by RNA interference Results: Minor changes (less than 0.4-fold) were observed in the amounts of mRNAs of Homo sapiens-specific Line-1 families in Hek293 Flp-IN T-Rex and PA-1 either overexpressing or depleted of TUTases and Mov10 Overall design: LINE-1 repetitive elements profiles of Hek293 Flp-IN T-Rex and PA-1 generated by deep sequencing, in triplicate, using Illumina NextSeq 500 and Illumina HiSeq 2500.
Publication Title
Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s.
Sample Metadata Fields
Cell line, Subject
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Choroid plexuses (CP) develop early during development. They form a barrier between the blood and the cerebrospinal fluid, and fulfill important protective and nutritive functions. We used Affymetrix microarrays to assess whether CP of the lateral ventricles (LVCP) have similar functions in developing and adult brain. We identified distinct families of protective and transport genes and found that most of these genes were already well expressed during development.
Publication Title
Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
To assay the effect of depletion of the RNA exosome on RNAs shorter than the standard length captured by RNA-seq (>200 nt), we created RNA-seq libraries using fragmented RNA and a linker-ligation-based protocol that does not deplete RNAs shorter than 200 nt. Note: these data relate to Figure 6E in Lubas, Andersen et al., Cell Reports 2014 (accepted) Overall design: These samples constitute RNA-seq libraries prepared to enrich for short RNA fragments such as snRNA and snoRNAs. Three different HeLa cell RNAi experiments were used to generate the RNA samples applied in the library construction: control transfected, hRRP40-depleted and triple-depleted of the known RNA exosome-associated ribonucleases (DIS3, DIS3L and hRRP6 knock-down). By these means the data offers reveal RNA exosome substrates via their up-regulation in the respective knock-downs NOTE: The ''Figure6E_RNAseq_DataTable_PlottedValues.txt'' was generated from total 5 samples, with two additional published samples [SRP031620] and provided to better allow readers to fully replicate the analyses presented in the publication.
Publication Title
The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- NextSeq 500
Description
In our studies we were searching for the new factors engaged in mitochondrial nucleic acids metabolism under stress conditions in humans. Quantitative proteomic approach revealed C6orf203 protein as a potential new factor engaged in response to perturbed mitochondrial gene expression. We showed that C6orf203 is a mitochondrial RNA binding protein which is able to rescue diminished mitochondrial transcription in stress conditions. Overall design: The dataset corresponds to RNAseq studies and comprises experiment performed in triplicate. The aim of this study was to examine the influence of C6orf203 silencing on mitochondrial transcriptome. To this end we engineered two stable cell lines with the use of human 293 Flp-In T-Rex cells as parental. First cell line inducible expressed miRNAs silencing endogenous copy of C6orf203 gene while second one expressed additionally transgenic version of FLAG-tagged C6orf203 which contained silent mutations causing insensitivity to miRNA. We also analyzed RNA isolated from parental 293 Flp-In T-Rex cells. RNAseq libraries were prepared with the use of strand-specific library preparation procedures. RNAs were random fragmented and reverse transcribed using random oligomers as primers (dUTP-based protocol, see PMID: 29590189, PMID: 22609201; this pipeline enables analysis of RNAs (> ~100 nucleotides)). RNA was isolated from unfractionated cells using TRI-Reagent. Before preparation of the libraries total RNA was subjected to depletion of nuclear-encoded rRNAs (Ribo-Zero rRNA Removal Kit (Human/Mouse/Rat), Epicenter). Libraries were sequenced with the help of Illumina sequencing platform.
Publication Title
Quantitative proteomics revealed C6orf203/MTRES1 as a factor preventing stress-induced transcription deficiency in human mitochondria.
Sample Metadata Fields
Specimen part, Subject
View Samples