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SRP124262
Mus musculus
75 Downloadable Samples
NextSeq 500, Illumina HiSeq 2500
Description
IL-7 regulates homeostatic mechanisms that maintain the overall size of the T cell pool throughout life. We show that, under steady-state conditions, IL-7 signaling is principally mediated by activation of signal transducers and activators of transcription 5 (STAT5). In contrast, under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1 and STAT5 activation. Consequently, the IL-7-induced transcriptome is altered with enrichment of IFN-stimulated genes (ISGs). Moreover, STAT1 overexpression was associated with reduced survival in CD4+ T cells undergoing lymphopenia-induced proliferation (LIP). We propose a model in which T cells undergoing LIP upregulate STAT1 protein, "switching on" an alternate IL-7-dependent program. This mechanism could be a physiological process to regulate the expansion and size of the CD4+ T cell pool. During HIV infection, the virus could exploit this pathway, leading to the homeostatic dysregulation of the T cell pools observed in these patients. Overall design: Sorted naive CD4 T and CD8 T cells from WT or STAT1 transgenic mice were stimulated for 90 minutes with IL-7 or IFNg. Additonally CD4 T cells from WT or STAT1 trangenic or IL7Ra449F transgenic mice were stimulated for overnight with IL-7 or IFNg or IFNa4. Up to four biological replicates tested for each condition.
Publication Title
IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Background: Changes in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a single Drosophila melanogaster tissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe. Results: Relatively few genes (<100) displayed sexually dimorphic expression in the brain, but there was an enrichment of sex-biased genes, especially male-biased genes, on the X chromosome. Over 340 genes differed in brain expression between flies from the African and European populations, with the between-population divergence being highly correlated between males and females. The differentially expressed genes include those involved in stress response, olfaction, and detoxification. Expression differences were associated with transposable element insertions at two genes implicated in insecticide resistance (Cyp6g1 and CHKov1). Conclusions: Analysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues. Overall design: mRNA profiles of Drosophila melanogaster brains from adult males and females from a European and an African population (2 biological replicates each)
Publication Title
Population and sex differences in Drosophila melanogaster brain gene expression.
Sample Metadata Fields
Sex, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Post-translational modifications of proteins by Small Ubiquitin-like Modifiers (SUMOs) regulate protein degradation and localization, protein-protein interaction, and transcriptional activity. SUMO E3 ligase functions are executed by SIZ1/SIZ2 in yeast and PIAS family members in human. The Arabidopsis genome contains only one gene, SIZ1, that is orthologous to yeast SIZ1/SIZ2. Here, we show that the Arabidopsis SIZ1 interacts with SUM1 and SCE1a, the SUMO E2 conjugating enzyme. Compared to WT, the null mutant siz-1-3 is smaller in statue because of reduced expression of gene involved in brassinosteroid biosynthesis and signalling. Drought stress induces the accumulation of SUMO-protein conjugates, which is in part dependent on SIZ1 but not on ABA. Mutant plants of siz1-3 have significant lower tolerance to drought stress. Genome wide expression analysis identified about 2,000 Arabidopsis genes that are responsive to drought, and SIZ1 mediates the induction of 600 of these genes by a pathway independent of DREB2A and ABA. SIZ1-dependent, drought-responsive genes include those encoding enzymes of the anthocyanin synthesis pathway and jasmonate response. From these results, we conclude that SIZ1 regulates Arabidopsis development and plays a role in drought stress response probably through the control of gene expression.
Publication Title
The Arabidopsis E3 SUMO ligase SIZ1 regulates plant growth and drought responses.
Sample Metadata Fields
Age
View Samples- Rattus norvegicus
- 40 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To identify genes important in fetal preparation for birth.
Publication Title
Developmental control of the Nlrp6 inflammasome and a substrate, IL-18, in mammalian intestine.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
We report the role of LSM1-7 complex in the Arabidopsis tolerance to abiotic stresses. LSM1-7 controls gene expression reprogramming at the post-transcriptional level by promoting the decapping of mRNA. This function is selectively achieve over selected stress-induced transcripts depending on stress nature. Overall design: Comparison of transcriptomes from Col-0 and lsm1a lsm1b plants exposed to low temperatures, drought or high salt conditions
Publication Title
The LSM1-7 Complex Differentially Regulates Arabidopsis Tolerance to Abiotic Stress Conditions by Promoting Selective mRNA Decapping.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the role of SmE1 protein in the control of Arabidopsis development and tolerance to abiotic stresses. SmE1 controls gene expression reprogramming at the post-transcriptional level by promoting the splicing of pre-mRNA. This function is selectively achieve over selected transcripts depending on the stimulus nature. Overall design: Transcriptomic profiling through RNAseq of Col-0 and sme1-1 plants under control conditions or exposed to low temperatures (4ºC, 24h)
Publication Title
Arabidopsis SME1 Regulates Plant Development and Response to Abiotic Stress by Determining Spliceosome Activity Specificity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Purpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome.
Publication Title
Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Understanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in 21st century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their mechanisms of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (MWCNTs; Mitsui-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP) was observed for MWCNTs at a biologically relevant dose (0.25 g/cm2) and for asbestos at 2 g/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature related to MWCNT- and asbestos-induced MMP. Fourty-nine of the MMP-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were associated with MMP and one of them, miR-1275, was found to negatively correlate with a large part of the MMP-associated genes. Cellular processes such as gluconeogenesis, glucose metabolism, mitochondrial LC-fatty acid -oxidation and spindle microtubule function were enriched among the MMP-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.
Publication Title
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The transcriptional regulator YAP orchestrates important cell functions, determining tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin cytoskeleton-dependent and Hippo kinase-independent mechanisms. RHO activity is necessary but not sufficient for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based siRNA screenings provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective ECM remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. Overall design: RNA-Seq in WT and Cav1KO mouse embryonic fibroblasts (MEFs) cultured on stiff or soft polyacrylamide hydrogels
Publication Title
Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples