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.
<i>Lactobacillus acidophilus</i> Attenuates <i>Salmonella</i>-Induced Stress of Epithelial Cells by Modulating Tight-Junction Genes and Cytokine Responses.
Sex, Cell line, Treatment, Subject
View SamplesGene 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.
Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders.
Age, Specimen part, Time
View SamplesPelizaeus-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.
Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model.
Sex, Age, Specimen part
View SamplesThe 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.
Arhgef12 drives IL17A-induced airway contractility and airway hyperresponsiveness in mice.
Sex, Age, Specimen part, Disease, Subject
View SamplesA 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)
A neuronal PI(3,4,5)P<sub>3</sub>-dependent program of oligodendrocyte precursor recruitment and myelination.
Sex, Age, Specimen part
View SamplesHmx1 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.
Identification of HMX1 target genes: a predictive promoter model approach.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.
Disease, Cell line
View SamplesTo explore the degree to which the glioma cell lines remained transcriptionally stable under diverse experimental conditions, we transplanted three different lines (U3020MG, U3047MG and U3065MG) intracranially to NOD-SCID mice; explanted the resulting tumors and cultured the cells for two passages, and then isolated RNA from the cell line prior to transplantation (U3020MG-p10, U3047MG-p7, U3065MG-p10), from the xenograft tumor and from the explanted cells.
The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.
Disease
View SamplesThe 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).
Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis.
Cell line
View SamplesTranscriptional programming of cell identity promises to open up new frontiers in regenerative medicine by enabling the efficient production of clinically relevant cell types. We examine if such cellular programming is accomplished by transcription factors that each have an independent and additive effect on cellular identity, or if programming factors synergize to produce an effect that is not independently obtainable. The combinations of Ngn2-Isl1-Lhx3 and Ngn2-Isl1-Phox2a transcription factors program embryonic stem cells to express a spinal or cranial motor neuron identity respectively. The two alternate expression programs are determined by recruitment of Isl1/Lhx3 and Isl1/Phox2a pairs to distinct genomic locations characterized by two alternative dimeric homeobox motifs. These results suggest that the function of programming modules relies on synergistic interactions among transcription factors and thus cannot be extrapolated from the study of individual transcription factors in a different cellular context.
Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity.
Cell line, Treatment
View Samples