The entorhinal cortex of the mouse seems to be sensitive to molecular mechanisms that have been linked to the pathology of Alzheimer's disease. In this microarray study we are interested in comparing the expression profile of the left versus the right EC of the mouse, in order to understand if there is a significant difference in gene expression that might reveal any insights into the differential activation of these areas.
Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease.
Age, Specimen part
View SamplesWe report an applicaton of small RNA sequencing using high throughput next generation sequencing to identify the small RNA content of cell lines. By sequencing over 30 million reads we could identify a new class of small RNAs previousy observed with tiling arrays and mapping to promoter regions of coding genes. We also identified a large number of small RNAs corresponding to internal exons of coding genes. By using different enzymatic treatments and immunoprecipitation experiments, we have determined that both the promoter associated small RNAs as well as ones within the body of the genes bear 5'' cap structures. Overall design: Examination of the expression of small RNAs (<200nt).
Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs.
No sample metadata fields
View SamplesWe report that the HF/HS-mediated functional enrichment of genes of immunity and inflammation is driven toward normal by the AOF supplementation Obesity may not constantly associate with metabolic disorders and mortality later in life, raising the challenging concept of healthy obesity. Here, high fat-high sucrose (HF/HS) feeding produces hyperglycaemia and hypercholesterolemia, increases oxidative stress, elevates endotoxemia, expands adipose tissue (with enlarged adipocytes, macrophage infiltration and accumulation of cholesterol and oxysterols), and reduces lifespan of obese mice. Despite persistence of obesity, supplementation with an antioxidant formulation normalizes plasma lipids and endotoxemia, prevents macrophage recruitment in adipose tissue, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends lifespan. The HF/HS-mediated functional enrichment of genes of immunity and inflammation (in particular response to lipopolysaccharides) is driven towards normal by the antioxidant formulation. It is concluded that the limitation of immune cell infiltration in adipose tissue on the long term by an antioxidant formulation can increase lifespan independently of body weight and fat storage. It constitutes the hallmark of a healthy adiposity trait. Overall design: Examination of the expression profile of mice adipose tissues fed either standard (Std), High-fat/high-sucrose (HF/HS) or HF/HS + antioxidant formulation (AOF) for 180 days
Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract.
Age, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with the deletion of a portion of the Alu element from MIR205HG transcript
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with MIR205HG knock-down in RWPE-1 cells
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
No sample metadata fields
View SamplesPeripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P=.01). High expression of cytotoxic genesignaturewithin the TBX21 subgroup also showed poor clinical outcome (P=.05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P=.004).
Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesHuman pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials, and offer a cost effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically-defined poly(ethylene glycol) (PEG) hydrogels and cultured in serum-free media to model cellular interactions of the developing brain. The precursors self-assembled into 3-dimensional (3D) neural constructs with cortically organized neuronal and glial cells, interconnected vascular networks, and ramified microglia. Replicate constructs were highly reproducible by RNA sequencing (Spearman's correlation coefficients, ? = 0.97) and robustly expressed neurogenesis, vasculature development, and microglia genes. Finally, linear support vector machines were used to construct a predictive model from RNA sequencing data for 240 neural constructs treated with 60 toxic and non-toxic chemicals, which then correctly classified 9/10 blinded compounds. Overall design: Note that all cell types were derived from the H1 human embryonic stem cell line. 11 samples for initial quality control (triplicate day 13 neural progenitor cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells and migroglia/macrophage precursor cells), quadruplicate samples of H1 ES cells as a control for comparing to untreated toxicity study samples, and 288 samples associated with toxicity screening (all samples formed using neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors).
Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques.
No sample metadata fields
View SamplesChromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those generated by the ENCODE project in nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (=3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched for important cell type-specific genes; and (iii) GWAS variants associated with traits relevant to a particular cell type are more enriched in stretch enhancers compared with short enhancers. Reporter constructs containing stretch enhancer sequences exhibited tissue-specific activity in cell culture experiments and in transgenic mice. These results suggest that stretch enhancers are critical chromatin elements for coordinating cell type-specific regulatory programs and that sequence variation in stretch enhancers affects risk of major common human diseases. Overall design: Integrated analysis of islet chromatin modification and transcriptome data with those generated by the ENCODE project. NISC Comparative Sequencing Program
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants.
No sample metadata fields
View SamplesSenescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-J? in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, and p53 activation provides a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effector genes and, in vivo, promotes tumour and stromal cell expansion. Together, the findings support a CAF activation/stromal evolution model under convergent CSL/p53 control. Overall design: Human Dermal Fibroblasts were transfected with two different siRNA against CSL in parallel with a control siRNA. Total RNA was extracted 3 days post-transfection, followed by RNA-Seq analysis.
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.
No sample metadata fields
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