Similar Datasets
Project description:Early stem cell differentiation programmes are tightly controlled by coordinated pre- and post-transcriptional regulatory networks. In this study, we investigate and characterise miRNA networks responsible for the post-translational gene regulation in early differentiation in both female and male mouse embryonic stem cells. We obtained miRNA-Seq and RNA-Seq profiles of male and female cells from day 0 (D0; 2i) to days 4, 10, 20 and 30. Interestingly, we observed a significant difference in gene expression profiles between females and males, both in terms of identity of regulated genes and of temporal characteristics. Similarly, we observed differences between miRNA species playing significant regulatory roles in female and male cells.
2018-12-31 | GSE77690 | GEO
Project description:Early stem cell differentiation programmes are tightly controlled by coordinated pre- and post-transcriptional regulatory networks. In this study, we investigate and characterise miRNA networks responsible for the post-translational gene regulation in early differentiation in both female and male mouse embryonic stem cells. We obtained miRNA-Seq and RNA-Seq profiles of male and female cells from day 0 (D0; 2i) to days 4, 10, 20 and 30. Interestingly, we observed a significant difference in gene expression profiles between females and males, both in terms of identity of regulated genes and of temporal characteristics. Similarly, we observed differences between miRNA species playing significant regulatory roles in female and male cells.
2018-12-31 | GSE77691 | GEO
Project description:miRNA regulatory networks in male and female mouse ESC-to-EpiSC differentiation
| PRJNA311215 | ENA
Project description:The function of metabolic state in stemness is poorly understood. Mouse embryonic stem cells (ESC) and epiblast stem cells (EpiSC) are at distinct pluripotent states representing the inner cell mass (ICM) and epiblast embryos. Human embryonic stem cells (hESC) are similar to EpiSC stage. We now show a dramatic metabolic difference between these two stages. EpiSC/hESC are highly glycolytic, while ESC are bivalent in their energy production, dynamically switching from glycolysis to mitochondrial respiration on demand. Despite having a more developed and expanding mitochondrial content, EpiSC/hESC have low mitochondrial respiratory capacity due to low cytochrome c oxidase (COX) expression. Similarly, in vivo epiblasts suppress COX levels. These data reveal EpiSC/hESC functional similarity to the glycolytic phenotype in cancer (Warburg effect). We further show that hypoxia-inducible factor 1? (HIF1?) is sufficient to drive ESC to a glycolytic Activin/Nodal-dependent EpiSC-like stage. This metabolic switch during early stem-cell development may be deterministic.
| S-EPMC3343469 | biostudies-literature
Project description:The requirements for self-renewal differ between EpiSCs and ES cells and the underlying mechanism is largely unknown. Here we show that mouse EpiSCs can be efficiently derived and robustly propagated even from single cells, using two small-molecule inhibitors: CHIR99021 and XAV939. The whole-genome microarray analyses is performed to confirm the identity of EpiSC maintained in CHIR/XAV by comparing the expression profile in EpiSC-CHIR/XAV to those in ESC maintained in 2i and EpiSC maintained in FGF2/activin.
2011-08-19 | GSE31461 | GEO
Project description:The requirements for self-renewal differ between EpiSCs and ES cells and the underlying mechanism is largely unknown. Here we show that mouse EpiSCs can be efficiently derived and robustly propagated even from single cells, using two small-molecule inhibitors: CHIR99021 and XAV939. The whole-genome microarray analyses is performed to confirm the identity of EpiSC maintained in CHIR/XAV by comparing the expression profile in EpiSC-CHIR/XAV to those in ESC maintained in 2i and EpiSC maintained in FGF2/activin. Total RNA from ESC-2i, EpiSC-CHIR/XAV, and EpiSC-FGF2/activin were extracted for microarray analisys
2011-08-18 | E-GEOD-31461 | biostudies-arrayexpress
Project description:Parkinson's disease (PD) is the second-most common neurodegenerative disease, and its pathophysiology is associated with alpha-synuclein accumulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. MicroRNAs are small non-coding RNAs that regulate gene expression, and many previous studies have described their dysregulation in plasma, CSF, and in the brain of patients with PD. In this study, we aimed to provide a regulatory network analysis on differentially expressed miRNAs in the brain of patients with PD. Based on our systematic review with a focus on the substantia nigra and the putamen, we found 99 differentially expressed miRNAs in brain samples from patients with PD, which regulate 135 target genes. Five genes associated with neuronal survival (BCL2, CCND1, FOXO3, MYC, and SIRT1) were modulated by dysregulated miRNAs found in the substantia nigra and the putamen of patients with PD. The functional enrichment analysis found FoxO and PI3K-AKT signaling as pathways related to PD. In conclusion, our comprehensive analysis of brain-related miRNA-mRNA regulatory networks in PD showed that mechanisms involving neuronal survival signaling, such as cell cycle control and regulation of autophagy/apoptosis, may be crucial for the neurodegeneration of PD, being a promising way for novel disease-modifying therapies.
| S-EPMC8228551 | biostudies-literature
Project description:MotivationMicroRNAs (miRNAs) play a key role in regulating tumor progression and metastasis. Identifying key miRNAs, defined by their functional activities, can provide a deeper understanding of biology of miRNAs in cancer. However, miRNA expression level cannot accurately reflect miRNA activity.ResultsWe developed a computational approach, ActMiR, for identifying active miRNAs and miRNA-mediated regulatory mechanisms. Applying ActMiR to four cancer datasets in The Cancer Genome Atlas (TCGA), we showed that (i) miRNA activity was tumor subtype specific; (ii) genes correlated with inferred miRNA activities were more likely to enrich for miRNA binding motifs; (iii) expression levels of these genes and inferred miRNA activities were more likely to be negatively correlated. For the four cancer types in TCGA we identified 77-229 key miRNAs for each cancer subtype and annotated their biological functions. The miRNA-target pairs, predicted by our ActMiR algorithm but not by correlation of miRNA expression levels, were experimentally validated. The functional activities of key miRNAs were further demonstrated to be associated with clinical outcomes for other cancer types using independent datasets. For ER(-)/HER2(-) breast cancers, we identified activities of key miRNAs let-7d and miR-18a as potential prognostic markers and validated them in two independent ER(-)/HER2(-) breast cancer datasets. Our work provides a novel scheme to facilitate our understanding of miRNA. In summary, inferred activity of key miRNA provided a functional link to its mediated regulatory network, and can be used to robustly predict patient's survival.Availability and implementationthe software is freely available at http://research.mssm.edu/integrative-network-biology/Software.html.Contactjun.zhu@mssm.eduSupplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC5006235 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-02-19 | E-GEOD-66027 | biostudies-arrayexpress
Project description:BackgroundAlthough the study of gene regulation via the action of specific microRNAs (miRNAs) has experienced a boom in recent years, the analysis of genome-wide interaction networks among miRNAs and respective targeted mRNAs has lagged behind. MicroRNAs simultaneously target many transcripts and fine-tune the expression of genes through cooperative/combinatorial targeting. Therefore, they have a large regulatory potential that could widely impact development and progression of diseases, as well as contribute unpredicted collateral effects due to their natural, pathophysiological, or treatment-induced modulation. We support the viewpoint that whole mirnome-transcriptome interaction analysis is required to better understand the mechanisms and potential consequences of miRNA regulation and/or deregulation in relevant biological models. In this study, we tested the hypotheses that ethanol consumption induces changes in miRNA-mRNA interaction networks in the mouse frontal cortex and that some of the changes observed in the mouse are equivalent to changes in similar brain regions from human alcoholics.ResultsmiRNA-mRNA interaction networks responding to ethanol insult were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Important pathways (coexpressed modular networks detected by WGCNA) and hub genes central to the neuronal response to ethanol are highlighted, as well as key miRNAs that regulate these processes and therefore represent potential therapeutic targets for treating alcohol addiction. Importantly, we discovered a conserved signature of changing miRNAs between ethanol-treated mice and human alcoholics, which provides a valuable tool for future biomarker/diagnostic studies in humans. We report positively correlated miRNA-mRNA expression networks that suggest an adaptive, targeted miRNA response due to binge ethanol drinking.ConclusionsThis study provides new evidence for the role of miRNA regulation in brain homeostasis and sheds new light on current understanding of the development of alcohol dependence. To our knowledge this is the first report that activated expression of miRNAs correlates with activated expression of mRNAs rather than with mRNA downregulation in an in vivo model. We speculate that early activation of miRNAs designed to limit the effects of alcohol-induced genes may be an essential adaptive response during disease progression.
| S-EPMC3924350 | biostudies-literature