This SuperSeries is composed of the SubSeries listed below.
Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia.
Specimen part
View SamplesThe aim of this study was to determine the role that miRNAs have on influencing murine microgial phenotypes under M1(LPS) and M2a (IL-4) stimulating conditions.
Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients.
Sex, Disease
View SamplesThe purpose of this study was to investigate the expression dynamics of mRNAs and microRNAs in response to subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) or relapsing-remitting type of the disease (RRMS).
MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients.
Sex, Disease
View SamplesTranslation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated. Overall design: 4-thiouridine (4su) metabolic labeling was performed on mouse embryonic stem cells (ESCs) and Epiblast like cells (EpiLCs).
Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells.
Specimen part, Disease, Subject
View SamplesThe role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) is not completely understood, particularly at the molecular level.
Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma.
Specimen part
View SamplesMitochondria are able to modulate cell state and fate during normal and pathophysiologic conditions through a nuclear mediated mechanism collectively termed as a retrograde response. Our previous studies in Drosophila have clearly established that progress through the cell cycle is precisely regulated by the intrinsic activity of the mitochondrion by specific signaling cascades mounted by the cell. As a means to further our understanding of how mitochondrial energy status affects nuclear control of basic cell decisions we have employed Affymetrix microarray-based transcriptional profiling of Drosophila S2 cells knocked down for the gene encoding subunit Va of the complex IV of the mitochondrial electron transport chain. The profiling data identifies up-regulation of glycolytic genes and metabolic studies confirm this increase in glycolysis. The transcriptional portrait which emerges implicates many signaling systems, including a p53 response, an insulin response, and up-regulation of conserved mitochondrial responses. This rich dataset provides many novel targets for further understanding the mechanism whereby the mitochondrion may direct cellular fate decisions. The data also provides a salient model of the shift of metabolism from a predominately oxidative state towards a predominately aerobic glycolytic state, and therefore provides a model of energy substrate management not unlike that found in cancer.
Expression profiling of attenuated mitochondrial function identifies retrograde signals in Drosophila.
Cell line
View SamplesBackground: Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling. Methods: Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization. Results: Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the 3 putative subclasses (ANOVA, Bonferonni correction, p < 0.05) identified 6,934 differentially regulated genes. K means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the 3 subclasses. Leave one out cross validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C. Conclusions: Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.
Identification of pediatric septic shock subclasses based on genome-wide expression profiling.
Age, Specimen part, Disease, Disease stage
View SamplesMouse oocyte maturation, fertilization, and reprogramming occur in the absence of transcription and thus must be regulated post-transcriptionally. Surprisingly, a major form of post-transcriptional regulation, microRNA-based transcript destabilization and translational inhibition, is lost during this developmental window. Here we evaluate the conservation, timing, and mechanism behind the loss of microRNA activity in oocytes. In both mouse and frogs, microRNA function was active in growing oocytes, but then lost during oocyte maturation. RNA-sequencing of the maturing oocytes uncovered expression of an alternative isoform of Ago2 lacking domains critical for its function. Introduction of full-length Ago2 together with an exogenous microRNA destabilized microRNA luciferase reporters. However, endogenous targets were still largely unaffected. These findings suggest that while it is possible to re-activate some aspects of microRNA activity by introducing full length Ago2, there are additional mechanisms to protect endogenous transcripts from microRNA activity in oocytes. Overall design: Total RNA from mouse GV and MII oocytes, embryonic stem cells, epi cells
Expression of Alternative Ago2 Isoform Associated with Loss of microRNA-Driven Translational Repression in Mouse Oocytes.
Specimen part, Subject
View SamplesBackground: Septic shock heterogeneity has important implications for the conduct of clinical trials and individual patient management. We previously addressed this heterogeneity by indentifying 3 putative subclasses of children with septic shock based on a 100-gene expression signature corresponding to adaptive immunity and glucocorticoid receptor signaling. Herein we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. Methods: Gene expression mosaics were generated from the 100 class-defining genes for 82 individual patients in the validation cohort. Patients were classified into 1 of 3 subclasses (A, B, or C) based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. Separate classifications were conducted by 21 individual clinicians and a computer-based algorithm. After subclassification the clinical database was mined for clinical phenotyping. Results: In the final consensus subclassification generated by clinicians, subclass A patients had a higher illness severity, as measured by illness severity scores and maximal organ failure, relative to subclasses B and C. The k coefficient across all possible inter-evaluator comparisons was 0.633. Similar observations were made based on the computer-generated subclassification. Patients in subclass A were also characterized by repression of a large number of genes having functional annotations related to zinc biology. Conclusions: We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses can be indentified by clinicians without formal bioinformatics training, at a clinically relevant time point, and have clinically relevant phenotypic differences.
The influence of developmental age on the early transcriptomic response of children with septic shock.
Age, Specimen part, Disease, Disease stage
View Samples