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GSE84495
Mus musculus
78 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways. The up-regulated Fgf21 levels in NAFLD were implied to be a protective response against the NAFLD-induced adverse effects, e.g. lipotoxicity, oxidative stress and endoplasmic reticulum stress. An in vivo PPARalpha challenge demonstrated the dysregulation of PPARalpha signalling in the presence of NAFLD, which resulted in a stochastically increasing hepatic expression of Fgf21. Notably, elevated plasma Fgf21 was associated with declining expression of Klb, Fgf21s crucial co-receptor, which suggests a resistance to Fgf21. Therefore, although liver fat accumulation is a benign stage of NAFLD, the elevated plasma Fgf21 likely indicated vulnerability to metabolic stressors that may contribute towards progression to end-stage NAFLD. In conclusion, plasma levels of Fgf21 reflect liver fat accumulation and dysregulation of metabolic pathways in the liver.
Publication Title
Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 106 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic and epigenetic regulation of gene expression in fetal and adult human livers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 106 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome wide expression analysis of 92 adult and 14 fetal liver samples
Publication Title
Genetic and epigenetic regulation of gene expression in fetal and adult human livers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 60 Downloadable Samples
Illumina HiSeq 2500
Description
Background and Purpose—Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. Methods—We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. Results—We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. Conclusions—For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture. Overall design: RNA sequencing of 44 intracranial aneurysm samples (including 21 unruptured, 22 ruptured and 1 undetermined) and 16 control samples of the intracranial cortical artery
Publication Title
RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Much is known concerning the cellular and molecular basis for CD8+ T memory immune responses. Nevertheless, conditions that selectively support memory generation have remained elusive. Here we show that an immunization regimen that delivers TCR signals through a defined antigenic peptide, inflammatory signals through LPS, and growth and differentiation signals through the IL-2R initially favors antigen-specific CD8+ T cells to rapidly and substantially develop into tissue-residing T effector-memory cells by TCR transgenic OVA-specific OT-I CD8+ T cells. Amplified CD8+ T memory development depends upon a critical frequency of antigen-specific T cells and direct responsiveness to IL-2. A homologous prime-boost immunization protocol with transiently enhanced IL-2R signaling in normal mice led to persistent polyclonal antigen-specific CD8+ T cells that supported protective immunity to Listeria monocytogenes. These results identify a general approach for amplified T memory development that may be useful to optimize vaccines aimed at generating robust cell-mediated immunity.
Publication Title
Transient enhanced IL-2R signaling early during priming rapidly amplifies development of functional CD8+ T effector-memory cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This study determined the genes that are differentially expressed when regulatory T cells (Tregs) were isolated from the lamina propria of the small and large intestine from mice with impaired IL-2R signaling (designated Y3) or impaired IL-2R signaling and lack of CD103 expression (designated Y3/CD103-/-) when compared to Tregs from WT mice. 204 unique annotated mRNAs were differentially expressed by 1.5 fold between these 3 groups (Fig. 6B). Very few mRNAs were uniquely up or down regulated in relationship to impaired IL-2R signaling or the combination of impaired IL-2R signaling and lack of CD103 expression. Thus, lack of CD103 does not obviously regulated signaling in Tregs in the gut mucosa and most differentially expressed genes were due to impaired IL_2R signaling. Gene enrichment analysis of these differentially expressed genes identified 4 major enrichment groups (EG) are: EG1, Cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway; EG2, regulation of lymphocyte activation and proliferation; EG3, regulation of cell death and the caspase pathway in apoptosis; and EG4, transcription.
Publication Title
IL-2Rβ-dependent signaling and CD103 functionally cooperate to maintain tolerance in the gut mucosa.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Displacement of Bromodomain and Extra-Terminal (BET) proteins from chromatin has promise for cancer and inflammatory disease treatments, but roles of BET proteins in metabolic disease remain unexplored. Small molecule BET inhibitors, such as JQ1, block BET protein binding to acetylated lysines, but lack selectivity within the BET family (Brd2, Brd3, Brd4, Brdt), making it difficult to disentangle contributions of each family member to transcriptional and cellular outcomes. Here, we demonstrate multiple improvements in pancreatic -cells upon BET inhibition with JQ1 or BET-specific siRNAs. JQ1 (50-400 nM) increases insulin secretion from INS-1 cells in a concentration dependent manner. JQ1 increases insulin content in INS-1 cells, accounting for increased secretion, in both rat and human islets. Higher concentrations of JQ1 decrease intracellular triglyceride stores in INS-1 cells, a result of increased fatty acid oxidation. Specific inhibition of both Brd2 and Brd4 enhances insulin transcription, leading to increased insulin content. Inhibition of Brd2 alone increases fatty acid oxidation. Overlapping yet discrete roles for individual BET proteins in metabolic regulation suggest new isoform-selective BET inhibitors may be useful to treat insulin resistant/diabetic patients. Results imply that cancer and diseases of chronic inflammation or disordered metabolism are related through shared chromatin regulatory mechanisms.
Publication Title
BET Bromodomain Proteins Brd2, Brd3 and Brd4 Selectively Regulate Metabolic Pathways in the Pancreatic β-Cell.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To investigate the role of p53 and DICER in the induction of ER stress, wildtype, p53 knockout or DICER mutant HCT116 colon cancer cells were treated with the ER stress inducers tunicamycin or brefeldin A for 24 hours.
Publication Title
A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Illumina HiSeq 1000
Description
Zinc is both an essential and potentially toxic metal. It is widely believed that oral zinc supplementation can reduce the effects of the common cold; however, there is strong clinical evidence that intranasal (IN) zinc gluconate (ZG) gel treatment for this purpose causes anosmia, or the loss of the sense of smell, in humans. Using the rat olfactory neuron cell line, Odora, we investigated the molecular mechanism by which zinc exposure exerts its toxic effects on olfactory neurons. Following treatment of Odora cells with 100 and 200 µM ZG for 0-24 h, RNA-seq and in silico analyses revealed up-regulation of pathways associated with zinc metal response, oxidative stress, and ATP production. We observed that Odora cells recovered from zinc-induced oxidative stress, but ATP depletion persisted with longer exposure to ZG. ZG exposure increased levels of NLRP3 and IL-1ß protein levels in a time-dependent manner, suggesting that zinc exposure may cause an inflammasome-mediated cell death, pyroptosis, in olfactory neurons. Overall design: 5 treatment groups, 3 replicates/group, 1 control group, 3 groups treated with 100 µM zinc gluconate for increasing time (6, 12, and 24 h), 1 group treated with 200 µM zinc gluconate for 6 h
Publication Title
Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This sudy focuses on the identification of transcripts in the shoot phloem of the model plant Arabidopsis thaliana. Transcripts expressed in the phloem tissue (parenchyma cell, companion cell, sieve element) were excised by laser microdissection pressure catapulting (LMPC). These were compared with transcripts isolated from leaf phloem exudates by EDTA-chelation technique. Optimization of sample harvest resulted in RNA of high quality from both sources. Modifications of the RNA amplification procedure obtained RNA of sufficient yield and quality for microarray experiments. Microarrays (Affymetrix, ATH1) hybridized with RNA derived from phloem tissue by LMPC or phloem sap allowed us to differentiate between phloem located and mobile transcript species. The datasets provide a search criterion for phloem-based signals and will facilitate reverse genetic studies and forward genetic screens for phloem and long distance RNA signaling mutants.
Publication Title
Identification of Arabidopsis thaliana phloem RNAs provides a search criterion for phloem-based transcripts hidden in complex datasets of microarray experiments.
Sample Metadata Fields
No sample metadata fields
View Samples