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GSE76896
Homo sapiens
200 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 99 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic islet beta cell failure causes type 2 diabetes (T2D). The IMIDIA consortium has used a strategy entailing a stringent comparative transcriptomics analysis of islets isolated enzymatically or by laser microdissection from two large cohorts of non-diabetic (ND) and T2D organ donors (OD) or partially pancreatectomized patients (PPP). This work led to the identification of a signature of genes that were differentially expressed between T2D and ND regardless of the sample type (OD or PPP). This signature includes 19 genes, of which 9 have never been previously reported to be differentially expressed in T2D islets. The PPP cohort also includes samples from individuals with impaired glucose tolerance (IGT) or recent onset diabetes associated with a pancreatic exocrine disorder (T3cD). Notably, none of the 19 signature genes of T2D islets were significantly dysregulated in islets of subjects with IGT or T3cD, suggesting that their changed expression reflects beta cell deterioration rather than a deficit preceding it.
Publication Title
Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 101 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic islet beta cell failure causes type 2 diabetes (T2D). The IMIDIA consortium has used a strategy entailing a stringent comparative transcriptomics analysis of islets isolated enzymatically or by laser microdissection from two large cohorts of non-diabetic (ND) and T2D organ donors (OD) or partially pancreatectomized patients (PPP). This work led to the identification of a signature of genes that were differentially expressed between T2D and ND regardless of the sample type (OD or PPP). This signature includes 19 genes, of which 9 have never been previously reported to be differentially expressed in T2D islets. The PPP cohort also includes samples from individuals with impaired glucose tolerance (IGT) or recent onset diabetes associated with a pancreatic exocrine disorder (T3cD). Notably, none of the 19 signature genes of T2D islets were significantly dysregulated in islets of subjects with IGT or T3cD, suggesting that their changed expression reflects beta cell deterioration rather than a deficit preceding it.
Publication Title
Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.
Sample Metadata Fields
Age
View Samples- Danio rerio
- 20 Downloadable Samples
IlluminaHiSeq1000, IlluminaGenomeAnalyzerIIx
Description
Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism. Overall design: RNA-Seq from total RNA of zebrafish larvae during (5 dpf) the diurnal cycle. Time-series mRNA profiles of untreated wild type (WT), rx3t25327/t25327 [rx3 strong] and rx3t25181/t25181 [rx3 weak] mutant larvae as well as dexamethasone treated WT and rx strong larvae were generated by deep sequencing.
Publication Title
Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Acute liver injury is a critical life-threatening event. Common causes are infections, intoxication, and ischemic conditions. The cytokine Interleukin 22 (IL-22) has been implicated in this process. However, the role of IL-22 during acute liver damage is controversial, since both protective and pathogenic properties have been reported. IL-22 binding protein (IL-22BP, IL-22Ra2), a soluble endogenous inhibitor of IL-22, is able to regulate IL-22 activity, and thus might explain some of the controversial findings. Since the role of IL-22BP in liver injury is unknown, we used Il22bp deficient mice and mouse models for acute liver damage to address this point. We found that Il22bp deficient mice were more susceptible to ischemia- and acetaminophen- induced liver damage. Deficiency of Il22bp caused increased hepatic damage and delayed liver regeneration. Using an unbiased approach, we found that IL-22, if uncontrolled in Il22bp deficient mice, induced Cxcl10 expression by hepatocytes, thereby recruiting inflammatory CD11b+Ly6C+ monocytes into the liver upon liver damage. Accordingly, neutralization of Cxcl10 reversed the increased disease susceptibility of Il22bp deficient mice. In conclusion, our data suggest dual functions of IL-22 in acute liver damage, and highlight the need to control IL-22 activity via IL-22BP. Overall design: RNA sequencing of RNA isolated from liver tissue from mice that underwent liver reperfusion treatment (IR) or sham surgery, in triplicate for three genotypes (Wt, Il22-/- and Il22bp-/-).
Publication Title
A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
To address the role of INO80/SWR-type remodeling complexes, we deleted Ep400 at defined times of mouse oligodendrocyte development. Whereas oligodendrocyte precursors are specified and develop normally without Ep400, terminal differentiation is dramatically impaired resulting in hypomyelination. RNA-Seq studies were performed on cultured and FACS sorted control and Ep400-deficient mouse oligodendrocytes to analyze changes in gene expression. These revealed that genes associated with the myelination program and with response to DNA damage are altered in Ep400-deficient oligodendrocytes. Overall design: OPC mRNA profiles of 6-day old control (ctrl) and Ep400 cko mice were generated using the Illumina HiSeq 2500 platform.
Publication Title
Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD69 is a transmembrane protein expressed on the surface of activated leukocyte. The ligand for CD69 and the intracellular signaling pathway of this molecule are yet unknown. It is widely used as a marker of activated lymphocyte, but its function in immune system is not known.
Publication Title
CD69 regulates type I IFN-induced tolerogenic signals to mucosal CD4 T cells that attenuate their colitogenic potential.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oral cancer kills about 1 person every hour each day in the United States and is the 6th most prevalent cancer worldwide. In this study we utilized existing microarray data from a prior oral cancer study to examine the role of chronic pro-inflammatory mediators in oral carcionogenesis by comparing gene expression in oral tumors with adjacent non-tumor oral tissue from the same patient
Publication Title
Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.
Sample Metadata Fields
Disease, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Research in human immunobiology is mainly based on working with peripheral blood mononuclear cells (PBMC). However, recent investigations have shown that circulating CD4+ T cells are less sensitive to several T-cell activating monoclonal antibodies (mAb) and to recall antigens as compared to tissue-resident cells or cells that were in-vitro cultured at a high cell density of 10^7 cells/mL for 2 days at 37C and 5% CO2 (RESTORE protocol, Rmer et al., Blood 2011, PMID: 21931118). To explain the increase in sensitivity of CD4+ T-cells to mAbs and recall antigens on a molecular level, we performed microarray hybridizations of total RNA from T-cells isolated from PBMC that were cultured at a low or high cell density. To avoid the detection of genes that are up- or down-regulated by the culture process itself, we used low cell density cultured PBMC, instead of freshly prepared PBMC.
Publication Title
High-density preculture of PBMCs restores defective sensitivity of circulating CD8 T cells to virus- and tumor-derived antigens.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
The cochlea possesses a robust circadian clock machinery that regulates auditory function. How the cochlear clock is influenced by the circadian system remains unknown. Here we show that cochlear rhythms are system-driven and require local Bmal1 as well as central input from the suprachiasmatic nuclei (SCN). SCN ablations disrupted the circadian expression of the core clock genes in the cochlea. Since the circadian secretion of glucocorticoids (GCs) is controlled by the SCN and that GCs are known to modulate auditory function, we assessed their influence on circadian gene expression. Removal of circulating GCs by adrenalectomy (ADX) did not have a major impact on core clock gene expression in the cochlea. Rather it abolished the transcription of clock-controlled genes involved in inflammation. ADX abolished the known differential auditory sensitivity to day and night noise trauma and prevented the induction of GABA-ergic and glutamate receptors mRNA transcripts. However, these improvements were unrelated to changes at the synaptic level suggesting other cochlear functions may be involved. Due to this circadian regulation of noise sensitivity by GCs, we evaluated the actions of the synthetic glucocorticoid dexamethasone (DEX) at different times of the day. DEX was effective in protecting from acute noise trauma only when administered during daytime, when circulating glucocorticoids are low, indicating that chronopharmacological approaches are important for obtaining optimal treatment strategies for hearing loss. GCs appear as a major regulator of the differential sensitivity to day or night noise trauma, a mechanism likely involving the circadian control of inflammatory responses. Overall design: Cochlear samples from sham operated or adrenalectomized (ADX) CBA/Sca mice were collected every 4th hour during a 24h period and subjected to RNAseq (n=3 per time point, corresponding to a total of 36 samples).
Publication Title
Circadian Regulation of Cochlear Sensitivity to Noise by Circulating Glucocorticoids.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples