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SRP110515
Caenorhabditis elegans
30 Downloadable Samples
Illumina HiSeq 2000
Description
HIV-1 nucleoside reverse transcriptase inhibitor (NRTI) use is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to NRTIs has predominantly been assigned to mitochondrial polymerase-? inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear. In this study we show that short-term effects of these drugs, which are rarely discussed in the literature, include direct inhibition of the mitochondrial respiratory chain (MRC), decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC), which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure. Overall design: RNA-seq on Caenorhabditis elegans exposed to DMSO, 3''-azido-3''-deoxythymidine (zidovudine or AZT), 2'',3''-didehydro-2'',3''-deoxythymidine (stavudine or d4T), 3''-deoxy-3''-fluorothymidine (alovudine or FLT) or untreated control after 24 or 72 hours of exposure.
Publication Title
Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We address the function of HEXIM, an inhibitor of the general transcriptional elongation regulator P-TEFb which regulates the transcriptional status of many developmental genes, during Drosophila development. We showed that HEXIM knockdown mutants display organs development failure. In the wing disc, it induces apoptosis and affects Hh signaling. The continuous death of proliferative cells is compensated by apoptosis-induced cell proliferation, in a manner similar to that of differentiated cells, together with high levels of Hh and Ci. We completed this analysis with microarrays to characterize the molecular phenotype of HEXIM knockdown during eye differentiation.
Publication Title
Functional Interaction between HEXIM and Hedgehog Signaling during Drosophila Wing Development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- NextSeq 500
Description
EMT, Epithelial to mesenchymal transition is a developmental biology process associated with migration, known to be involved in cancer metastasis. To study this process, we used the breast epithelial cell line MCF10A that enter in EMT after treatment with the cytokine TGFB or by expression of EMT transcriptor factor SNAIL. Overall design: mRNA profiles of MCF10A cells treated for 1 or 6 days with TGFb (done in duplicate), and mRNA profiles of Snail inducible line, MCF10A-SNAIl, induced for 1 or 6 days.
Publication Title
Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 86 Downloadable Samples
- Illumina HiSeq 2000
Description
Huntington’s disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models and PDE10 loss may represent a homeostatic adaptation to maintain signaling. Elevation of both cAMP and cGMP by PDE10 inhibition were required for rescue. Phosphoproteomic profiling of striatum in response to PDE10 inhibition highlighted plausible neural substrates responsible for the improvement. Early chronic PDE10 inhibition in Q175 mice showed improvements beyond those seen with acute administration after symptom onset, including partial reversal of striatal deregulated transcripts and the prevention of the emergence of HD neurophysiological deficits. Overall design: Transcriptional profiling of cortex and striatal tissue following chronic dosing of either vehicle or the PDE10A inhibitor PF-02545920 (0.32, 1 and 3.2 mg/kg po qd) in the Q175 homozygous knock-in mouse model of Huntington’s disease (dosing from 5-weeks to 9 months of age).
Publication Title
Phosphodiesterase 10A Inhibition Improves Cortico-Basal Ganglia Function in Huntington's Disease Models.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment, Subject
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used Affymetrix Arabidopsis ATH1 GeneChip to profile RNAs active in wild type columbia (glabrous) and CaMV::DME pollen and stamens.
Publication Title
Identification of putative Arabidopsis DEMETER target genes by GeneChip analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Bos taurus
- 49 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Mastitis in dairy cows is one of the most costly and prevalent diseases affecting dairy cows world wide. Insight in the molecular regulation of the host immune response to an E. coli infection, could help to develop new strategies to prevent cattle from E. coli infection. Here we performed a gene-expression analysis from udder tissue exposed to a controlled E. coli infection at T=24h post infection (p.i.) representing the acute phase response and at T=192h p.i. representing a chronic stage.
Publication Title
In depth analysis of genes and pathways of the mammary gland involved in the pathogenesis of bovine Escherichia coli-mastitis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Glycine max
- 26 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
We microdissected each compartment from 6-micron paraffin sections using the Leica AS LMD system to identify all genes active in different compartments of a soybean seed containing globular-stage embryos.
Publication Title
Using genomics to study legume seed development.
Sample Metadata Fields
No sample metadata fields
View Samples