Transcriptome analysis of LPS-stimulated bone marrow-derived dendritic cells with NR4A3 gene silencing
The Orphan Nuclear Receptor NR4A3 Is Involved in the Function of Dendritic Cells.
Specimen part
View SamplesXBP1 is a transcription factor that is induced by unconventional splicing associated with endoplasmic reticulum stress and plays a role in development of liver and plasma cells. We previously reported that brain derived neurotrophic factor (BDNF) leads to splicing of XBP1 mRNA in neurites, and that XBP1 is required for BDNF-induced neurite extension and branching. To search for the molecular mechanisms of how XBP1 plays a role in neural development, comprehensive gene expression analysis was performed in primary telencephalic neurons obtained from Xbp1 knockout mice at embryonic day 12.5. By searching for the genes induced by BDNF in wild type neurons but this induction was reduced in Xbp1 knockout mice, we found that upregulation of three GABAergic markers, somatostatin (Sst), neuropeptide Y (Npy), and calbindin (Calb1), were compromised in Xbp1 knockout neurons. Attenuated induction of Npy and Calb1 was confirmed by quantitative RT-PCR. In neurons lacking in Xbp1, upregulation of GABAergic markers was attenuated. Impaired BDNF-induced neurite extension in Xbp1 knockout neurons might be mediated by disturbed BDNF-induced differentiation of GABAergic interneurons.
Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1.
Specimen part
View SamplesSaccharomyces cerevisiae flocculation occurs when fermentable sugars are limiting and is therefore considered as a way to enhance the survival chance of Flo-expressing yeast cells. In this paper, the role of Flo1p in mating was demonstrated by showing that the mating efficiency, which contributes to the increased survival rate as well by generating genetic variability, is increased when cells flocculate. This was revealed by liquid growth experiments in a low shear environment and differential transcriptome analysis of FLO1 expressing cells compared to the non-flocculent wild-type cells. The results show that a floc provides a uniquely organized multicellular ultrastructure that provides a suitable microenvironment to induce and perform cell conjugation.
Molecular mechanism of flocculation self-recognition in yeast and its role in mating and survival.
No sample metadata fields
View SamplesBy silencing of RALA, a downstream member of the RAS signal transduction pathway, we aimed to determine whether genes downstream of a mutated KRAS (codon 12 or 13) or a mutated BRAF can have significant functions in colorectal cancer carcinogenesis.
Effects of RAL signal transduction in KRAS- and BRAF-mutated cells and prognostic potential of the RAL signature in colorectal cancer.
Specimen part, Cell line, Treatment
View SamplesNeuregulin-1 (NRG-1) is a paracrine factor critical for cardiac development. We have been examining whether the recombinant NRG-1 isoform known as glial growth factor 2 (GGF2) has therapeutic potential for heart failure. In both small and large animals after experimental myocardial infarction (MI) we have found that GGF2 treatment improves myocardial function and limits progressive myocardial remodeling. To understand potential mechanisms for this effect, we compared gene expression in swine by microarray analysis.
Anti-remodeling and anti-fibrotic effects of the neuregulin-1β glial growth factor 2 in a large animal model of heart failure.
Specimen part, Disease, Treatment
View SamplesPurpose: Mutations in several genetic loci lead to cardiac anomalies, with mutations in transcription factor NKX2-5 gene being one of the largest mutations known. Gestational hypoxia, such as seen in high-altitude pregnancy, has been known to affect cardiac development, and this paper aims to uncover information about the underlying mechanisms of this phenomena. Methods: Wild-type female mice were mated with Nkx2-5 mutant males, to produce offsprings. The pregnant females were then separated into two groups, one left in normal air and one breathing hypoxic, 14% oxygen, air from gestation day 10.5 to 12.5. Hearts were dissected from E12.5 embryos, subjected to RNA purification followed by RNA-seq. Wild-hypoxia and mutant-normoxia were compared to control wild-normoxia. Conclusions: The results of our study provide insights into a common molecular mechanism underlying non-genetic/epigenetic and genetic cardiac anomalies. Overall design: Embryonic mice were produced with either wild-type or mutant genomes, and some from each group were exposed to hypoxia during gestation, then physical analysis and RNA sequencing was done on the embryos.
Mechanism Sharing Between Genetic and Gestational Hypoxia-Induced Cardiac Anomalies.
Specimen part, Treatment, Subject
View SamplesAbstract: Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assess the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community to lack a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria show increased susceptibility to metabolic disease. Furthermore, bacterially-induced reduction of methyl-donor availability alters global DNA methylation patterns in both adult mice and their offspring in utero and engenders anxious behavior. Altogether, our results reveal an underappreciated aspect of bacterial choline metabolism (i.e., methyl-donor depletion) that is linked to alterations in metabolism, epigenetics, and behavior. More broadly, this work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal levels of nutrient intake. Overall design: 8 samples in total (biological n=4 per for each defined community; 9kw old female C57BL/6 mouse liver; 2 weeks of colonization and maintenance on 1% choline diet; 4hours of fasting prior to sacrifice)
Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption.
Cell line, Subject
View SamplesBackground: Humans with metabolic and inflammatory diseases frequently harbor lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Results: We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary components to (i) impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization, (ii) improve intestinal barrier function, (iii) lower systemic inflammation and (iv) ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate improves gut barrier function and reduces atherosclerosis development. Conclusions: Altogether, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis. Overall design: Intestinal mRNA profiles of gnotobiotic ApoE KO mice colonized with "core" community or "core plus Roseburia intestinalis" were generated by deep sequencing using Illumina HiSeq.
Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model.
Age, Specimen part, Subject
View SamplesSleep and affective behaviors are highly interrelated phenotypes, commonly altered in a variety of neuropsychiatric diseases, including major depressive disorder (MDD). To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J x 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions, including the frontal cortex, hippocampus, thalamus, and hypothalamus. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Utilizing publicly available transcriptomic datasets collected from sleep-deprived mice and major depressive disorder (MDD) patients, we identified three cortical gene networks altered by sleep/wake changes and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity-dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.
Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma.
Specimen part, Cell line
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