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GSE74240
Homo sapiens
6 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Novel strategies are needed to modulate -cell differentiation and function as potential -cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on cells was incompletely defined. We find that isoxazole largely induced genes that support neuroendocrine and -cell phenotypes, and suppressed a set of genes important for proliferation. Isoxazole alters -cell metabolites and protects glucose-responsive signaling pathways under lipotoxic conditions. Finally, we show that isoxazole improves glycemia in a mouse model of -cell regeneration. Isoxazole is a prime candidate for altering cell fate in different contexts.
Publication Title
Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Beneficial microbes can be actors in maintaining or stimulating barrier function, and may counteract pathogen-infection. Lactobacilli are particularly recognized for enhancing intestinal barrier function and to confer protective effects against multiresistant pathogens. Various L. acidophilus strains support intestinal immune barrier function and have been shown to improve resistance to pathogens. Although less extensively studied than beneficial bacteria, other food-based ingredients that can contribute to strengthening barrier function are dietary fibers. For instance, inulin and fructooligosaccharides (FOS) have recently been shown to enhance barrier function and protect against barrier dysfunction. Effects of these ingredients on intestinal barrier function were evaluated by quantifying regulation of gene expression by microarray. Methods: Caco-2 cells were incubated with probiotic strains or inulin-type fibers for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. Results: Only L. acidophilus modulated a group of 26 genes related to tight-junctions. Inulin-type fructans, L. brevis W63 and L. casei W56 regulated other genes, unrelated to tight junctions. L. acidophilus also had unique effects on a group of 6 genes regulating epithelial phenotype towards follicle-associated epithelium. L. acidophilus W37 was therefore selected for a challenge with STM and prevented STM-induced barrier disruption and decreased secretion of IL-8. L. acidophilus W37 increases TEER and can protect against STM induced disruption of gut epithelial cells integrity in vitro. Conclusion: Our results suggest that selection of specific bacterial strains for enforcing barrier function may be a promising strategy to reduce or prevent STM infections.
Publication Title
<i>Lactobacillus acidophilus</i> Attenuates <i>Salmonella</i>-Induced Stress of Epithelial Cells by Modulating Tight-Junction Genes and Cytokine Responses.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
Illumina HiSeq 2000
Description
The goal of the was to evaluate the mRNA expression profile of non-asthmatic and asthmatic airway smooth muscle. Overall design: RNA Seq was performed on nonasthmatic (n=5 individuals) and asthmatic (n=5 individuals) human airway smooth muscle cells.
Publication Title
Arhgef12 drives IL17A-induced airway contractility and airway hyperresponsiveness in mice.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Gene expression in forebrain structures change during day and night depending on circadian and rest-activity cycles. Clock genes have been shown to be involved in the control of circadian and sleep-wake control.
Publication Title
Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease, characterized by ataxia, intellectual disability, epilepsy and premature death. In the majority of cases, PMD is caused by duplication of PLP1 that is expressed in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is presently no curative therapy for PMD. We used a Plp1 transgenic PMD mouse model to test the therapeutic effect of Lonaprisan, an antagonist of the nuclear progesterone receptor, in lowering Plp1 mRNA overexpression. We applied placebo-controlled Lonaprisan therapy to PMD mice for 10 weeks and performed the grid slip analysis to assess the clinical phenotype. Additionally, mRNA expression and protein accumulation as well as histological analysis of the central nervous system were performed. While Plp1 mRNA levels are increased about 1.8-fold in PMD mice compared to wildtype controls, daily Lonaprisan treatment reduced overexpression at the RNA level up to 1.5-fold, which was sufficient to significantly improve a poor motor phenotype. Electron microscopy confirmed a 25% increase in the number of myelinated axons in the corticospinal tract when compared to untreated PMD mice. Microarray analysis revealed the upregulation of pro-apoptotic genes in PMD mice that could be partially rescued by Lonaprisan treatment, which also reduced microgliosis, astrogliosis, and lymphocyte infiltration.
Publication Title
Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hmx1 is a transcription factor expressed in the developing eye and ear and in some other parts of the nervous system. Dumbo mice are carrying the Hmx1 p.Q64X loss-of-function mutation (Munroe et al., 2009. BMC Developmental Biology). Transcriptomic analyses of this mouse model allows to decipher biological pathways under the control of Hmx1. In our study, we used it to better understand the role of Hmx1 in the retina and to identify several of its target genes.
Publication Title
Identification of HMX1 target genes: a predictive promoter model approach.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study is part of a larger multidisciplinary study entitled A dormant sub-population expressing interleukin-1 receptor characterises anti-estrogen resistant ALDH+ breast cancer stem cells.
Publication Title
Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDH<sup>+</sup> Breast Cancer Stem Cells.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
A neuronal PI(3,4,5)P3-dependent program of oligodendrocyte precursor recruitment and myelination was identified in mice that conditionally lack PTEN in cerebellar granular cells (PTEN cKO)
Publication Title
A neuronal PI(3,4,5)P<sub>3</sub>-dependent program of oligodendrocyte precursor recruitment and myelination.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of this study is to profile gene expression dynamics during the in vitro differentiation of embryonic stem cells into ventral motor neurons. Expression levels were profiled using Affymetrix microarrays at six timepoints during in vitro differentiation: ES cells (Day 0), embryoid bodies (Day 2), retinoid induction of neurogenesis (Day 2 +8hours of exposure to retinoic acid), neural precursors (Day 3), progenitor motor neurons (Day 4), postmitotic motor neurons (Day 7).
Publication Title
Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a major role in responding to injury or infection as well as immune response, inflammation, and hematopoiesis. High levels of circulating IL-6 are observed in many tumor types and are associated with poor outcomes. We show that knockdown of IL-6 or IL-6 receptor (IL-6R) inhibits IL-6 signaling and cell viability. In contrast, over-expression of IL-6 enhances tumor growth in vitro and in vivo, thereby supporting the role of IL-6 in tumorigenesis. We developed a human monoclonal antibody against human IL-6 (MEDI5117) that bears Fc mutations (YTE) to extend its half-life. We tested this antibody in several cancer cell lines that secrete high levels of IL-6, soluble IL-6R, and express gp130. High constitutive pSTAT3 (phosphorylated signal transducer and activator of transcription 3) activation is seen in several of these cell lines, suggesting autocrine growth stimulation by IL-6. Treating these cell lines with MEDI5117 effectively blocked phosphorylation of STAT3 and inhibited IL-6-induced cell proliferation. In vivo, MEDI5117 suppressed the growth of multiple cancer xenograft models and specifically modulated IL-6 signaling and downstream gene expression. Combining MEDI5117 with chemotherapy or gefitinib demonstrated significantly enhanced anti-tumor activities in vivo. Taken together, our data suggest that IL-6 signaling contributes to tumor growth, thereby supporting the development of MEDI5117 as a therapy to treat solid tumors.
Publication Title
A Novel IL6 Antibody Sensitizes Multiple Tumor Types to Chemotherapy Including Trastuzumab-Resistant Tumors.
Sample Metadata Fields
Specimen part
View Samples