Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia
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ABSTRACT:
ORGANISM(S): synthetic construct Mus musculus
PROVIDER: GSE49331 | GEO | 2014/03/13
SECONDARY ACCESSION(S): PRJNA213637
REPOSITORIES: GEO
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Project description:Neuroinflammation contributes to many neurologic disorders including Alzheimer's disease, multiple sclerosis, and stroke. Microglia is brain resident myeloid cells and have emerged as a key driver of the neuroinflammatory responses. MicroRNAs (miRNAs) provide a novel layer of gene regulation and play a critical role in regulating the inflammatory response of peripheral macrophages. However, little is known about the miRNA in inflammatory activation of microglia. To elucidate the role that miRNAs have on microglial phenotypes under classical (M1) or alternative (M2) activation under lipopolysaccharide ('M1'-skewing) and interleukin-4 ('M2a'-skewing) stimulation conditions, we performed microarray expression profiling and bioinformatics analysis of both mRNA and miRNA using primary cultured murine microglia. miR-689, miR-124, and miR-155 were the most strongly associated miRNAs predicted to mediate pro-inflammatory pathways and M1-like activation phenotype. miR-155, the most strongly up-regulated miRNA, regulates the signal transducer and activator of transcription 3 signaling pathway enabling the late phase response to M1-skewing stimulation. Reduced expression in miR-689 and miR-124 are associated with dis-inhibition of many canonical inflammatory pathways. miR-124, miR-711, miR-145 are the strongly associated miRNAs predicted to mediate anti-inflammatory pathways and M2-like activation phenotype. Reductions in miR-711 and miR-124 may regulate inflammatory signaling pathways and peroxisome proliferator-activated receptor-gamma pathway. miR-145 potentially regulate peripheral monocyte/macrophage differentiation and faciliate the M2-skewing phenotype. Overall, through combined miRNA and mRNA expression profiling and bioinformatics analysis we have identified six miRNAs and their putative roles in M1 and M2-skewing of microglial activation through different signaling pathways.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-03-13 | E-GEOD-49331 | biostudies-arrayexpress
Project description:The 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. This Series includes expression data obtained from miRNA gene expression microarrays; mRNA expression profiles obtained from the same RNA samples were deposited as a separate Series. 9 total samples were analyzed, n=3 for the three stimulating conditions (resting state, LPS and IL-4) for murine primary microglia. This allowed us to perform the following pairwise comparisons: PBS vs. LPS, and PBS vs. IL-4. This was performed for both mRNA and miRNA gene expression profiles.
2014-03-13 | E-GEOD-49330 | biostudies-arrayexpress
Project description:The 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. This Series includes expression data obtained from mRNA gene expression microarrays; miRNA expression profiles obtained from the same RNA samples were deposited as a separate Series. 9 total samples were analyzed, n=3 for the three stimulating conditions (resting state, LPS and IL-4) for murine primary microglia. This allowed us to perform the following pairwise comparisons: PBS vs. LPS, and PBS vs. IL-4. This was performed for both mRNA and miRNA gene expression profiles.
2014-03-13 | E-GEOD-49329 | biostudies-arrayexpress
Project description:The 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. This Series includes expression data obtained from miRNA gene expression microarrays; mRNA expression profiles obtained from the same RNA samples were deposited as a separate Series.
2014-03-13 | GSE49330 | GEO
Project description:The 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. This Series includes expression data obtained from mRNA gene expression microarrays; miRNA expression profiles obtained from the same RNA samples were deposited as a separate Series.
2014-03-13 | GSE49329 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-10-08 | GSE62037 | GEO
Project description:Several studies have investigated miRNA and mRNA co-expression to identify regulatory networks at the transcriptional level. A typical finding of these studies is the presence of both negative and positive miRNA-mRNA correlations. Negative correlations are consistent with the expected, faster degradation of target mRNAs, whereas positive correlations denote the existence of feed-forward regulations mediated by transcription factors. Both mechanisms have been characterized at the molecular level, although comprehensive methods to represent miRNA-mRNA correlations are lacking. At present, genome-wide studies are able to assess the expression of more than 1000 mature miRNAs and more than 35,000 well-characterized human genes. Even if studies are generally restricted to a small subset of genes differentially expressed in specific diseases or experimental conditions, the number of potential correlations remains very high, and needs robust multivariate methods to be conveniently summarized by a small set of data.Nonparametric Kendall correlations were calculated between miRNAs and mRNAs differentially expressed in livers of patients with acute liver failure (ALF) using normal livers as controls. Spurious correlations due to the histopathological composition of samples were removed by partial correlations. Correlations were then transformed into distances and processed by multidimensional scaling (MDS) to map the miRNA and mRNA relationships. These showed: (a) a prominent displacement of miRNA and mRNA clusters in ALF livers, as compared to control livers, indicative of gene expression dysregulation; (b) a clustering of mRNAs consistent with their functional annotations [CYP450, transcription factors, complement, proliferation, HLA class II, monocytes/macrophages, T cells, T-NK cells and B cells], as well as a clustering of miRNAs with the same seed sequence; and (c) a tendency of miRNAs and mRNAs to populate distinct regions of the MDS plot. MDS also allowed to visualize the network of miRNA-mRNA target pairs.Different features of miRNA and mRNA relationships can be represented as thematic maps within the framework of MDS obtained from pairwise correlations. The symmetric distribution of positive and negative correlations between miRNA and mRNA expression suggests that miRNAs are involved in a complex bidirectional molecular network, including, but not limited to, the inhibitory regulation of miRNA targets.
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Project description:Increasing amounts of evidence indicate that noncoding RNAs (ncRNAs) have important roles in various biological processes. Here, miRNA, lncRNA, and mRNA expression profiles were analyzed in human HepG2 and L02 cells using high-throughput technologies. An integrative method was developed to identify possible functional relationships between different RNA molecules. The dominant deregulated miRNAs were prone to be downregulated in tumor cells, and the most abnormal mRNAs and lncRNAs were always upregulated. However, the genome-wide analysis of differentially expressed RNA species did not show significant bias between up- and downregulated populations. miRNA-mRNA interaction was performed based on their regulatory relationships, and miRNA-lncRNA and mRNA-lncRNA interactions were thoroughly surveyed and identified based on their locational distributions and sequence correlations. Aberrantly expressed miRNAs were further analyzed based on their multiple isomiRs. IsomiR repertoires and expression patterns were varied across miRNA loci. Several specific miRNA loci showed differences between tumor and normal cells, especially with respect to abnormally expressed miRNA species. These findings suggest that isomiR repertoires and expression patterns might contribute to tumorigenesis through different biological roles. Systematic and integrative analysis of different RNA molecules with potential cross-talk may make great contributions to the unveiling of the complex mechanisms underlying tumorigenesis.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2022-03-03 | GSE162997 | GEO