Similar Datasets
Project description:MicroRNAs (miRNAs) regulate many neurodevelopmental events, including proliferation, neurogenesis, neuronal migration, and cell survival. Individual miRNAs interact with hundreds of mRNA transcripts, but the precise landscape of these interactions in the context of cell-type-specificity has not been determined. Here, we used multiple parallel approaches, including AGO2-HITS-CLIP, combined mRNA and miRNA single-cell profiling and bipartite network analysis, to reveal a non-uniformity of miRNA-mRNA interactions that supports both defined cell-type identities as well as their dynamic transitions during human brain development at stages of peak neurogenesis. miRNA-mRNA clusters dynamically exploit the redundancy of the miRNA target code to differentially cluster across transitions in brain development. Using cell-type-specific functional properties of miRNA-mRNA interactions, we identify the role of great ape-specific miR-2115 in regulating cortical progenitor cell proliferation by targeting a radial glia enriched gene, origin recognition complex subunit 4 (ORC4). Together, our study suggests that miRNAs contribute to cell identity by regulating the expression of cell-type-specific transcripts.
2018-11-21 | GSE107467 | GEO
Project description:MicroRNAs (miRNAs) regulate many neurodevelopmental events, including proliferation, neurogenesis, neuronal migration, and cell survival. Individual miRNAs interact with hundreds of mRNA transcripts, but the precise landscape of these interactions in the context of cell-type-specificity has not been determined. Here, we used multiple parallel approaches, including AGO2-HITS-CLIP, combined mRNA and miRNA single-cell profiling and bipartite network analysis, to reveal a non-uniformity of miRNA-mRNA interactions that supports both defined cell-type identities as well as their dynamic transitions during human brain development at stages of peak neurogenesis. miRNA-mRNA clusters dynamically exploit the redundancy of the miRNA target code to differentially cluster across transitions in brain development. Using cell-type-specific functional properties of miRNA-mRNA interactions, we identify the role of great ape-specific miR-2115 in regulating cortical progenitor cell proliferation by targeting a radial glia enriched gene, origin recognition complex subunit 4 (ORC4). Together, our study suggests that miRNAs contribute to cell identity by regulating the expression of cell-type-specific transcripts.
2018-11-21 | GSE107466 | GEO
Project description:Dynamic microRNA regulatory networks in establishing the Cellular specificity of developing human brains
| PRJNA420192 | ENA
Project description:Dynamic microRNA regulatory networks in establishing the Cellular specificity of developing human brains (miRNA-seq)
| PRJNA420199 | ENA
Project description:Dynamic microRNA regulatory networks in establishing the Cellular specificity of developing human brains (mRNA-seq)
| PRJNA420200 | ENA
Project description:The latest meta-analysis of genome-wide association studies identified 90 independent variants across 78 genomic regions associated with Parkinson's disease, yet the mechanisms by which these variants influence the development of the disease remains largely elusive. To establish the functional gene regulatory networks associated with Parkinson's disease risk variants, we utilized an approach combining spatial (chromosomal conformation capture) and functional (expression quantitative trait loci) data. We identified 518 genes subject to regulation by 76 Parkinson's variants across 49 tissues, whicih encompass 36 peripheral and 13 CNS tissues. Notably, one-third of these genes were regulated via trans-acting mechanisms (distal; risk locus-gene separated by >1 Mb, or on different chromosomes). Of particular interest is the identification of a novel trans-expression quantitative trait loci-gene connection between rs10847864 and SYNJ1 in the adult brain cortex, highlighting a convergence between familial studies and Parkinson's disease genome-wide association studies loci for SYNJ1 (PARK20) for the first time. Furthermore, we identified 16 neurodevelopment-specific expression quantitative trait loci-gene regulatory connections within the foetal cortex, consistent with hypotheses suggesting a neurodevelopmental involvement in the pathogenesis of Parkinson's disease. Through utilizing Louvain clustering we extracted nine significant and highly intraconnected clusters within the entire gene regulatory network. The nine clusters are enriched for specific biological processes and pathways, some of which have not previously been associated with Parkinson's disease. Together, our results not only contribute to an overall understanding of the mechanisms and impact of specific combinations of Parkinson's disease variants, but also highlight the potential impact gene regulatory networks may have when elucidating aetiological subtypes of Parkinson's disease.
| S-EPMC9373962 | biostudies-literature
Project description:Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.
| S-EPMC10983939 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-04-06 | GSE79046 | GEO
Project description:The regulation of gene expression in cells, including by microRNAs (miRNAs), is a dynamic process. Current methods for identifying miRNA targets by combining sequence and miRNA and mRNA expression data do not adequately use the temporal information and thus miss important miRNAs and their targets. We developed the MIRna Dynamic Regulatory Events Miner (mirDREM), a probabilistic modeling method that uses input-output hidden Markov models to reconstruct dynamic regulatory networks that explain how temporal gene expression is jointly regulated by miRNAs and transcription factors. We measured miRNA and mRNA expression for postnatal lung development in mice and used mirDREM to study the regulation of this process. The reconstructed dynamic network correctly identified known miRNAs and transcription factors. The method has also provided predictions about additional miRNAs regulating this process and the specific developmental phases they regulate, several of which were experimentally validated. Our analysis uncovered links between miRNAs involved in lung development and differentially expressed miRNAs in idiopathic pulmonary fibrosis patients, some of which we have experimentally validated using proliferation assays. These results indicate that some disease progression pathways in idiopathic pulmonary fibrosis may represent partial reversal of lung differentiation.
| S-EPMC3785769 | biostudies-literature
Project description:The oxytocin receptor (OTR) plays critical roles in social behavior development. Despite its significance, brain-wide quantitative understanding of OTR expression remains limited in postnatally developing brains. Here, we develop postnatal 3D template brains to register whole brain images with cellular resolution to systematically quantify OTR cell densities. We utilize fluorescent reporter mice (Otrvenus/+) and find that cortical regions show temporally and spatially heterogeneous patterns with transient postnatal OTR expression without cell death. Cortical OTR cells are largely glutamatergic neurons with the exception of cells in layer 6b. Subcortical regions show similar temporal regulation except the hypothalamus and two hypothalamic nuclei display sexually dimorphic OTR expression. Lack of OTR expression correlates with reduced dendritic spine densities in selected cortical regions of developing brains. Lastly, we create a website to visualize our high-resolution imaging data. In summary, our research provides a comprehensive resource for postnatal OTR expression in the mouse brain.
| S-EPMC7171089 | biostudies-literature