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SRP065840
Mus musculus
26 Downloadable Samples
Illumina HiSeq 2000
Description
RNA editing is a mutational mechanism that specifically alters the nucleotide content in sets of transcripts while leaving their cognate genomic blueprint intact. Editing has been detected from bulk RNA-seq data in thousands of distinct transcripts, but apparent editing rates can vary widely (from under 1% to almost 100%). These observed editing rates could result from approximately equal rates of editing within each individual cell in the bulk sample, or alternatively, editing estimates from a population of cells could reflect an average of distinct, biologically significant editing signatures that vary substantially between individual cells in the population. To distinguish between these two possibilities we have constructed a hierarchical Bayesian model which quantifies the variance of editing rates at specific sites using RNA-seq data from both single cells and a cognate bulk sample consisting of ~ 106 cells. The model was applied to data from murine bone-marrow derived macrophages and dendritic cells, and predicted high variance for specific edited sites in both cell types tested. We then 1 validated these predictions using targeted amplification of specific editable transcripts from individual macrophages. Our data demonstrate substantial variance in editing signatures between single cells, supporting the notion that RNA editing generates diversity within cellular populations. Such editing-mediated RNA-level sequence diversity could contribute to the functional heterogeneity apparent in cells of the innate immune system. Overall design: 26 samples were subjected to RNA-seq: 24 single WT macrophages, and 2 bulk samples (Apobec1 WT and KO macrophages), consisting of 500,000-1 million cells each.
Publication Title
RNA editing generates cellular subsets with diverse sequence within populations.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Danio rerio
- 6 Downloadable Samples
Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
Microcystin-LR (MC-LR), the most toxic member of microcystin family, inhibits protein phosphatase PP2A, triggers oxidative stress and induces hepatotoxicity. Gene expression profiling of MC-LR treated larvae using DNA microarray analysis revealed effects in the retinal visual cycle and pigmentation synthesis pathways that have not been previously associated with MC-LR. Liver-related genes were also differentially expressed. The microarray data were confirmed by quantitative real-time PCR. Our findings provide new evidence that microcystin-LR exposure of zebrafish larvae modulates the retinal visual cycle and pigmentation synthesis pathways and ultimately alter larval zebrafish behavior
Publication Title
Transcriptional and Behavioral Responses of Zebrafish Larvae to Microcystin-LR Exposure.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 5 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
We have characterised the zebrafish ortholog, setb, and investigated its role in embryogenesis. Phylogenetic analysis showed that zebrafish Setb has an amino acid sequence identity of approximately 96% with the mammalian orthologs. Whole mount immunofluorescence analysis revealed that Setb is expressed mainly in the eye, the lateral line neuromasts and the olfactory pit. Knockdown of setb using antisense morpholino oligonucleotides resulted in increased apoptosis, reduced cell proliferation and severe morphological defects. The morphant phenotypes were partially rescued when setb MO1 was co-injected with human set mRNA. In vivo labelling of hair cells in the lateral line of setb morphants with the vital fluorescent dye FM1-43 showed a significant decreased number of functional neuromasts. Gene expression analysis of setb morphants, employing DNA microarrays revealed a role of Setb in neurogenesis and the mechanosensory lateral line system.
Publication Title
The zebrafish homologs of SET/I2PP2A oncoprotein: expression patterns and insights into their physiological roles during development.
Sample Metadata Fields
Treatment
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Assessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress.
Publication Title
Deficiency in the α1 subunit of Na+/K+-ATPase enhances the anti-proliferative effect of high osmolality in nucleus pulposus intervertebral disc cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The metabolic syndrome (MetS) is characterized by the presence of metabolic abnormalities that include abdominal obesity, dyslipidemia, hypertension, increased blood glucose/insulin resistance, hypertriglyceridemia and increased risk for cardiovascular disease (CVD). The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model manifests several features of the MetS upon high fat diet (HFD) feeding. Moreover, the physiological changes in the white adipose tissue (WAT) contribute to MetS comorbidities. The aim of this study was to identify transcriptomic signatures in the gonadal WAT of ApoE3L.CETP mice in discrete stages of diet-induced MetS.
Publication Title
Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Promyelocytic Leukemia Protein (PML) was first identified as a fusion product with the retinoic acid receptor alpha in Acute Promyelocytic Leukemia (APL). Although PML has previously been studied in cancer progression and various physiological processes, little is known about its functions in Embryonic Stem Cells (ESC). Here, we report that PML contributes to the maintenance of the ESC self-renewal by controlling the cell-cycle and sustaining the expression levels of crucial pluripotency factors. Transcriptomic analysis showed that the ablation of PML renders ESC prone to exit from the nave and acquire a primed-like pluripotent cell state. During differentiation PML influences cell fate decision by regulation of Tbx3. PML loss compromises the reprogramming ability of embryonic fibroblasts to induced Pluripotent Stem Cells (iPSC) by inhibiting the TGF pathway at the very early stages. Collectively, these results designate PML as a member of the regulatory network for ESC pluripotency and somatic cell reprogramming.
Publication Title
Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
We generated de novo induced pluripotent stem cells (iPSCs) from two Parkinson’s Disease patients (PD) harboring the p.A53T mutation. iPSC-derived mutant neurons displayed disease-relevant phenotypes at basal conditions, including protein aggregation, compromised neuritic outgrowth and contorted axons with swollen varicosities containing aSyn and tau. We have performed RNA Sequencing (RNA-Seq) of neurons from PD patient and control samples. RNA sequencing has also been performed to neurons derived from HUES samples subjected to the same differentiation protocol as reference. Overall design: We have performed RNA Sequencing (RNA-Seq) in neurons PD and control samples (two clones from each individual), along with HUES-derived neurons.
Publication Title
Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson's disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2000
Description
We have ablated TAF10 in the erythroid compartment only by crossing the TAF10lox mice with the EpoR-Cre mice and we have studied the development of the erythroid cells in vivo. TAF10 ablation led to embryonic death at E13.5 while at E12.5 there was a clear developmental defect which was reflected in the transcriptional profile of the fetal liver cells. Gata1-target genes were mostly affected and were responsible for the lethal phenotype. Overall design: mRNA from E12.5 fetal livers of TAF10lox/KO:EpoR-Cre+/- (TAF10KO) mice, TAF10HET and WT mice was profiled by NGS (Illumina).
Publication Title
TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 17 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The liver plays a central role in vertebrate glucose homeostasis, and is also one of the most sexually dimorphic organs in terms of gene expression. While the extent of hepatic sexual dimorphism has been well described in mammals, little is known regarding this phenomenon in non-mammalian species, particularly fish. In this study, we examined hepatic gene expression and physiological phenotypes (growth, proximate body composition, retention efficiencies) to determine whether male and female zebrafish respond differently to diets comprised of 0, 15, 25, or 35 % carbohydrate. Using both Affymetrix microarrays and qRTPCR, we observed substantial sexual dimorphism in the hepatic transcriptome, and the response of some genes to dietary carbohydrate manipulation also varied by sex. Males upregulated genes associated with oxidative metabolism, carbohydrate metabolism, energy production, and amelioration of oxidative stress, while females had higher expression levels of genes associated with translation. Males also expressed elevated levels of hnf4a, a gene thought to be involved in regulating hepatic sexual dimorphism in the rodent. Dietary carbohydrate affected hepatic gene expression, growth performance, retention efficiencies of protein and energy, and percentage of moisture, lipid, and ash. Significant diet effects reflected differences between the 0% carbohydrate diet and the other diets, consistent with previous work on other cyprinids showing a high tolerance for dietary carbohydrate. Our data support the use of the zebrafish as a model for the study of both normal and disease states associated with carbohydrate metabolism, and highlight the importance of accounting for both sex and diet
Publication Title
Sexual dimorphism in hepatic gene expression and the response to dietary carbohydrate manipulation in the zebrafish (Danio rerio).
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 35 Downloadable Samples
- Illumina HiSeq 2000
Description
The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor. Overall design: mRNA profiles of whole Drosophila melanogaster adult males from an African, American, Asian and European population after infection with Beauveria bassiana. Samples include uninfected controls, 8h after infection and 24h after infection. 3 biological replicates each (2 in the case of American controls).
Publication Title
Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples