-cell identity is determined by tightly regulated transcriptional networks that are modulated by extracellular cues, thereby ensuring -cell adaptation to the organisms insulin demands. We have observed in pancreatic islets that stimulatory glucose concentrations induced a gene profile that was similar to that of freshly isolated islets, indicating that glucose-elicited cues are involved in maintaining -cell identity. Low glucose induces the expression of ubiquitous genes involved in stress responses, nutrient sensing, and organelle biogenesis. By contrast, stimulatory glucose concentrations activate genes with a more restricted expression pattern (- and neuronal- cell identity). Consistently, glucose-induced genes are globally reduced in islets deficient with Hnf1a (MODY3), characterized by a deficient glucose metabolism. Of interest, a cell cycle gene module was the most enriched among the variable genes between intermediate and stimulatory glucose concentrations. Glucose regulation of the islet transcriptome was unexpectedly broadly maintained in islets from aged mice. However, the cell cycle gene module is selectively lost in old islets and the glucose activation of this module is not recovered even in the absence of the cell cycle inhibitor p16.
Glucose regulation of a cell cycle gene module is selectively lost in mouse pancreatic islets during ageing.
Specimen part
View SamplesWe used microarrays to compare the global programme of gene expression in primary cultures of neurons and astrocytes. These data sets were compared to the expression profiles of other tissues, including pancreatic islets, in order to identify a specific neuroendocrine program in pancreatic islets.
Glucose regulation of a cell cycle gene module is selectively lost in mouse pancreatic islets during ageing.
Specimen part
View SamplesIslet amyloid polypeptide (IAPP) is the main component of amyloid deposits in type 2 diabetic patients. Cells overexpressing the human transcript of IAPP (hIAPP) present defects in insulin secretion.
Inhibition of BACE2 counteracts hIAPP-induced insulin secretory defects in pancreatic β-cells.
No sample metadata fields
View SamplesJarid2, a member of the Jumanji family of proteins, is a developmental regulator that is necessary for proper mouse development and stem cell differentiation. To investigate the specific functions of Jarid2 during pancreas development, we generated pancreas-specific Jarid2 mutants.
Late-stage differentiation of embryonic pancreatic β-cells requires Jarid2.
Specimen part
View SamplesBisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences of the exposure to bisphenol-A during development in pancreatic beta-cell growth
Maternal Exposure to Bisphenol-A During Pregnancy Increases Pancreatic β-Cell Growth During Early Life in Male Mice Offspring.
Sex, Specimen part
View SamplesNF-kB has been linked to doxorubicin-based chemotherapy resistance in breast cancer patients. NF-kB nuclear translocation and DNA binding in doxorubicin treated-breast cancer cells have been extensively examined, however its functional consequences in terms the spectrum of NF-kB -dependent genes expressed and, thus, the impact on tumour cell behaviour are unclear.
Deficiency in p53 is required for doxorubicin induced transcriptional activation of NF-кB target genes in human breast cancer.
Cell line, Treatment
View SamplesBackground: Interval breast cancers can occur through failure to detect an abnormality at the time of screening (missed interval cancer), or as a new event after a negative screen (true interval cancer). The development and progression of true interval tumors (TIBC) is known to be different than screen-detected tumors (SDBC). However, much work still needs to be done to understand the biological characteristics and clinical behaviour of these TIBC. Objectives: To characterize the gene expression profile in TIBC and SDBC aimed to identify biological markers that may be associated with the emergence of symptomatic breast cancer in the screening interval. Material and Methods: An unsupervised exploratory gene expression profile analysis was performed among 10 samples (discovery set, TIBC=5 and SDBC=5) using Affymetrix Human Gene 1.0 ST arrays and interpreted by Ingenuity Pathway Analysis. Differential expression of selected genes was confirmed in validation series of 91 patients (TIBC=12 and SDBC=79) by immunohistochemistry and 24 patients (TIBC=8 and SDBC=16) by RT-qPCR, expanding the analysis to other genes in same pathway (mTOR, 4E-BP1, eIF-4G and S6).
Gene expression profiling in true interval breast cancer reveals overactivation of the mTOR signaling pathway.
Specimen part
View SamplesAQM shows acute muscle wasting and weakness. Key aspects of AQM include muscle atrophy and myofilament loss. Gene expression profiling, using muscle biopsies from AQM, neurogenic atrophy and normal controls, showed that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways while only the AQM shows a specific strong induction of transforming growth factor (TGF)-beta/MAPK pathways.
Constitutive activation of MAPK cascade in acute quadriplegic myopathy.
No sample metadata fields
View SamplesThe goal of this study was to compare the transcriptional profile (RNA-seq) of imbibed Arabidopsis thaliana Columbia-0 ecotype seeds that were treated with a 20 min red or far red pulse. The red-light pulse induces germination. Overall design: Col-0 seeds were sown in clear plastic boxes, each containing 10 mL of 0.8 % (w/v) agar in demineralized water. To establish a minimum and equal photo-equilibrium, seeds were imbibed for 2 hours in darkness and then irradiated for 20 min with a saturated far-red pulse (FRp, calculated Pfr/P= 0.03, 42 µmol.m-2.s-1) in order to minimize the quantities of Pfr formed during their development in the mother plant. Seeds were then stratified at 5 °C in darkness for 3 days, prior to the 20 minutes with a saturated red pulse (Rp, calculated Pfr/P= 0.87, 0.05 µmol.m-2.s-1) or FRp. Three biological replicates of each condition were collected 12 hours after the corresponding R and FR light pulses.
Alternative Splicing Regulation During Light-Induced Germination of <i>Arabidopsis thaliana</i> Seeds.
Subject
View Samples2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic disease, diabetes, infertility and cancer. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 253 differentially modulated probe sets, identifying 217 well-characterized genes. A large part of these were associated with cell adhesion and/or angiogenesis and with transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway, were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34+ cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems.
Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects.
Specimen part, Treatment
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