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GSE68317
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The NF-B pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic beta cell dysfunction in the metabolic syndrome. While canonical NF-B signaling is well studied, there is little information on the divergent non-canonical NF-B pathway in the context of pancreatic islet dysfunction in diabetes. Here, we demonstrate that pharmacological activation of the non-canonical NF-B inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. Further, we identify NIK as a critical negative regulator of beta cell function as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of non-canonical NF-B components p100 to p52, and accumulation of RelB. Tumor necrosis factor (TNF) and receptor activator of NF-B ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive beta cell intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the non-canonical NF-B transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to beta cell failure. These studies reveal that NIK contributes a central mechanism for beta cell failure in diet-induced obesity.
Publication Title
Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adipose tissue iNKT cells have different functions than iNKT cells in the blood and other organs.
Publication Title
Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
NextSeq 500
Description
RNA sequencing of PLZF+ and PLZF- ?d T cell subsets from adipose tissue for gene expression analysis Overall design: PLZF+ and PLZF- ?d T cells were sorted from adipose tissue of PLZF-GFP mice for subsequent RNA sequencing and gene-expression analysis. Two replicates for each subset pooled from 10 mice each were used for the study.
Publication Title
γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 1492 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 357 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An International Multi-Center Study to Define the Clinical Utility of MicroarrayBased Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study)
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 204 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An international standardization program towards the application of gene expression profiling in routine leukaemia diagnostics: The MILE study pre-phase.
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets led to hyperphagia, obesity and reduced lifespan. These effects were not due to elevated BCAA per se or hepatic mTOR activation, but rather the shift in balance between dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and was linked to central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averted the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes were not due to intrinsic toxicity; rather, to hyperphagia driven by AA imbalance. Overall design: 3 animals per sex per diet were used. Mice were fed one of four diets (all 19% total protein, 63% carbohydrate, 18% fat, total energy density 14 kJ/g) varying in BCAA content (BCAA200: twice BCAA content of control diet AIN93G; BCAA100: standard content of BCAAs; and BCAA50 and BCAA20: containing one half and one fifth of standard content of BCAAs), and either euthanized at 15 months of age or maintained for determination of lifespan.
Publication Title
Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We analyed the gene expression profiles after knocking down MYCN or TFAP4. Results showed that transcription factor MYCN and TFAP4 commonly regulats a subset of genes that may contribute to neuroblastoma cells proliferation and migration.
Publication Title
MYCN promotes neuroblastoma malignancy by establishing a regulatory circuit with transcription factor AP4.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. Using a MYC target gene signature that predicts poor neuroblastoma prognosis we identified the histone chaperone, FAcilitates Chromatin Transcription (FACT), as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small molecule Curaxin compound, CBL0137, markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with chemotherapy in standard use by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN amplified neuroblastoma cells and a treatment strategy for MYCN-driven neuroblastoma
Publication Title
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Sample Metadata Fields
Cell line, Treatment
View Samples