Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a miRNA through their binding sites and that changes in ceRNA abundances from individual genes can modulate the miRNA’s activity. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target-site abundance through expression of a miR-122 target in hepatocytes and livers, and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target-site abundance (=1.5x10^5 added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target-site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect. Overall design: Seventeen mRNA profiles were generated of 1) primary hepatocytes of mice expressing variable levels of a recombinant Adenovirus expressing the transcript of AldolaseA (Ad-AldoA), containing either 1 or 3 sites matching miR-122 or a mutated miR-122 site (no site), 2) primary hepatocytes derived from mice treated with Antagomir-122 (treatment group) or Antagomir-122mm (control group), 3) livers originating of a genetic model (Ldlr deficient mice) causing severe pathological changes in cholesterol metabolism, 4) livers of mice perfused with Insulin or PBS, and 5) livers of mice fed a high-fat or chow diet; most samples were sequenced in duplicate or triplicate by an Illumina HiSeq 2000. One small RNA profile was also generated from livers of mice fed a chow diet by Solexa sequencing.
Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance.
No sample metadata fields
View SamplesWe report the transcriptome of single pancreatic cells at embryonic day e13.5 Overall design: Single cells mRNA of wild-type mouse pancreata at embryonic day 13.5
Single cell transcriptomic profiling of mouse pancreatic progenitors.
Specimen part, Cell line, Subject
View SamplesUsing a novel class of chemically-engineered oligonucleotides, termed "antagomirs", we studied the biological significance of silencing miR-122 in the liver of mice at the mRNA level
Silencing of microRNAs in vivo with 'antagomirs'.
No sample metadata fields
View SamplesRNA seq was performed comparing SC-specific Dicer mutants with SC-specific Lin28B transgenics to obtain an unbiased list of potentially de-regulated miRNA target candidates. Overall design: total RNA from sciatic nerves of P1 Dicer mutants, P1 Lin28 transgenics and their respective controls was used to perform RNA sequencing analysis.
The Lin28/let-7 axis is critical for myelination in the peripheral nervous system.
No sample metadata fields
View SamplesWe report the impact of heterozygous loss of either Pdx1 or Oc1 on the developing pancreas at e15.5 Overall design: mRNA of mouse pancreata at embryonic day 15.5 from control, Pdx1Lac/+, Oc1+/- and double heterozygous (Pdx1LacZ/+;Oc1+/-) embryos
Threshold-Dependent Cooperativity of Pdx1 and Oc1 in Pancreatic Progenitors Establishes Competency for Endocrine Differentiation and β-Cell Function.
Specimen part, Cell line, Subject
View SamplesTranscriptional and posttranscriptional regulatory networks play a crucial role in the maintenance and adaptation of pancreatic beta-cell function. In this study we show that the levels of the prototypic neuroendocrine miRNA-7 are regulated in islets of obese, diabetic and aged mouse models. Using gain- and loss-of-function models we demonstrate that miR-7 regulates crucial members of the endocrine pancreatic transcriptional network controlling differentiation and insulin synthesis. Importantly, it also directly regulates key proteins in the insulin granule secretory machinery. These results reveal an interconnecting miR-7 genomic circuit that influences beta-cell differentiation, insulin synthesis and release and define a role for miR-7 as an endocrine checkpoint to stabilize beta-cell function during metabolic stress. These findings have implications for miR-7 inhibitors as potential therapies for type 2 diabetes and neurodegenerative diseases.
MicroRNA-7a regulates pancreatic β cell function.
Specimen part, Cell line, Treatment
View SamplesMajor depression is a multidimensional disorder highly prevalent in modern society. Although several classes of antidepressants (ADs) are currently available to treat depression, the effectiveness of treatment is still limited, as many patients do not show full remission; thus, there is a need to find better patients directed therapeutic strategies. Neuroplastic changes in several brain regions, namely in the hippocampal dentate gyrus (DG), are amongst the best correlates of depression and of ADs actions. In this study the targets and molecular mediators of chronic stress and of four ADs from different pharmacological classes (fluoxetine, imipramine, tianeptine and agomelatine) were investigated in the DG.
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus.
Sex, Age, Specimen part
View SamplesInsulin resistance represents a hallmark during the development of type 2 diabetes mellitus (T2D) and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism 1,2,3. MicroRNA (miR)-dependent posttranscriptional gene silencing has recently been recognized to control gene expression in disease development and progression including that of insulin-resistant T2D. MiRs, whose deregulation alters hepatic insulin sensitivity include miR-143, miR-181 and miR-103/107. Here we report that expression of miR-802 is increased in liver of two obese mouse models and of obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, while reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b as a target of miR-802-dependent silencing and shRNA-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signaling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in db/db mice. Thus, the present study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism via targeting Hnf1b and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.
Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function.
Specimen part
View SamplesWe have analyzed gene expression in cone photoreceptors isolated from wild type and C-DGCR8 (DiGeorge Syndrome Critical Region Gene 8) KO mice at five different time points to get a mechanistic inside into the altered molecular pathways after microRNAs depletion.
miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function.
Specimen part
View Samples