Transcriptome analyses reveal enrichment of specific lncRNAs in specific brain regions and neuronal populations
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61401 | GEO | 2015/03/06
SECONDARY ACCESSION(S): PRJNA260988
REPOSITORIES: GEO
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Project description:Profiling of LncRNAs and mRNAs in the mouse pilocarpine model in specific brain regions, the hippocampus and cortex, and compared the results to those of the control mouse.
2017-10-06 | E-MTAB-5995 | biostudies-arrayexpress
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine. mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.
2016-07-27 | E-GEOD-81672 | biostudies-arrayexpress
Project description:A few reports have implicated specific lncRNAs in cardiac development or failure, but precise details of lncRNAs expressed in hearts and how their expression may be altered during embryonic heart development or by adult heart disease is unknown. By comparing lncRNA profiles of normal embryonic (~E14), normal adult, and hypertrophied adult hearts we defined a distinct fetal lncRNA abundance signature that includes 157 lncRNAs differentially expressed compared to adults (fold-change ≥ 50%, FDR=0.02), and which was only poorly recapitulated in hypertrophied hearts (17 differentially expressed lncRNAs; 13 of these observed in embryonic hearts). Analysis of protein-coding mRNAs from the same samples identified 22 concordantly and 11 reciprocally regulated mRNAs within 10 kb of dynamically expressed lncRNAs, reciprocal relationships of lncRNA and mRNA levels was validated for the Mccc1 and Relb genes using in vitro lncRNA knockdown in C2C12 cells. Network analysis suggested a central role for lncRNAs in modulating NFkappaB- and CREB1-regulated genes during embryonic heart growth and identified multiple mRNAs within these pathways that are also regulated, but independently of lncRNAs. Cardiac polyadenylated RNA (mRNA and lncRNA) profiles were generated from C57BL/6J mouse hearts were generated on Illumina HiSeq 2000 instruments. 7 independent E13.5 hearts, 12 adult hearts (6 at 6 weeks of age, 6 at 16 weeks of age), 4 sham-operated hearts at 12 weeks of age, and 4 hearts after 4 weeks of pressure overload (TAC) at 12 weeks of age.
2014-06-14 | E-GEOD-58455 | biostudies-arrayexpress
Project description:Major depressive disorder (MDD) strikes women twice as often as men, yet the molecular mechanisms contributing to this sex difference are poorly understood. Here, we explored the regulation of long noncoding RNAs (lncRNAs) in human postpartum brain tissue and found a robust baseline sex difference in lncRNA expression levels that is profoundly lost in MDD. We highlight one such lncRNA, that is upregulated in females with MDD, therefore we named FEDORA. FEDORA arose in humans and is expressed primarily in oligodendrocytes as well as in neurons. We tested FEDORA’s causal role in MDD, by utilizing a cell-type-specific approach to express it in the prefrontal cortex (PFC) of mice of both sexes. We found that expressing FEDORA in either neurons or oligodendrocytes promoted depression-like behaviors in females only, which mirrored the human sex-specific phenotype. These behavioral changes were associated with cell-type-specific changes in electrophysiological properties, myelin thickness, and gene expression. Finally, we found that blood FEDORA levels have diagnostic and prognostic features only for women with MDD. Together, these findings suggest that lncRNAs play key roles in shaping the sex-specific landscape of the brain and contribute to sex differences in MDD.
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Project description:We aimed to decipher the spatial expression landscape of well-annotated lncRNAs in brain regions. To this end, we dissected adult male mice brain tissues from olfactory bulb (OB), hypothalamus (Hypo), hippocampus (Hippo) and cerebellum (Cereb) and subjected to Arraystar Mouse LncRNA Microarray V3.0. We found a new type of genome organization formed by highly conserved lncRNA cluster and nearby TF in the non-imprinting regions that is associated with human CNS disorders.
2019-07-26 | GSE106832 | GEO
Project description:The eukaryotic genome has vast intergenic regions containing transposons, pseudogenes and other repetitive sequences. They produce numerous long non-coding RNAs (lncRNAs) and PIWI-interacting RNAs (piRNAs), yet the functions of the vast intergenic regions remain largely unknown. Mammalian piRNAs are abundantly expressed in late spermatocytes and round spermatids. Their expression coincides with the widespread expression of lncRNAs from the genome of these cells. Here, we show that piRNAs mediate the degradation of a large number of mRNAs and lncRNAs in mouse late spermatocytes. In particular, they have a large impact on the lncRNA transcriptome, as a quarter of lncRNAs expressed in late spermatocytes are upregulated in mice deficient in piRNA pathway. Furthermore, our genomic and in vivo functional analyses reveal that retrotransposon sequences in the 3´UTR of mRNAs are potentially targeted by piRNAs for degradation. Similarly, a large number of spermatogenic cell-specific lncRNAs are degraded by piRNAs via retrotransposon sequences. Moreover, we show that pseudogenes regulate mRNA stability via the piRNA pathway. The degradation of mRNAs and lncRNAs by piRNAs requires MIWI and, at least in part, depends on its slicer activity. Together, these findings reveal the presence of the highly complex and global RNA regulatory network mediated by piRNAs with retrotransposons and pseudogenes as regulatory sequences. RNA-seq of MIWI-immunoprecipitated RNAs from Late spermatocytes in Miw+/-, MiwiADH/-, Miwi-/-
2014-11-20 | E-GEOD-62416 | biostudies-arrayexpress
Project description:To improve our understanding of lncRNA expression in T cells, we used whole genome sequencing (RNA-seq) to identify lncRNAs expressed in human T cells and those selectively expressed in T cells differentiated under TH1, TH2, or TH17 polarizing conditions. The majority of these lineage-specific lncRNAs are co-expressed with lineage-specific protein-coding genes. These lncRNAs are predominantly intragenic with co-expressed protein-coding genes and are transcribed in sense and antisense orientations with approximately equal frequencies. Further, genes encoding TH lineage specific mRNAs are not randomly distributed across the genome but are highly enriched in the genome in genomic regions also containing genes encoding TH lineage-specific lncRNAs. Our analyses also identify a cluster of antisense lncRNAs transcribed from the RAD50 locus that are selectively expressed under TH2 polarizing conditions and co-expressed with IL4, IL5 and IL13 genes. Depletion of these lncRNAs via selective siRNA treatment demonstrates the critical requirement of these lncRNAs for expression of the TH2 cytokines, IL-4, IL-5 and IL-13. Collectively, our analyses identify new lncRNAs expressed in a TH lineage specific manner and identify a critical role for a cluster of lncRNAs for expression of genes encoding TH2 cytokines. Human peripheral blood mononuclear cells (PBMC) were cultured under TH1, TH2, and TH17 polarizing conditions. TH1, TH2, and TH17 primary and effector cultures were isolated and poly(A)+ and total RNA sequencing performed.
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Project description:In this research, we investigated the abnormal expression of lncRNA and established lncRNA-associated ceRNA regulatory networks composed of potential therapeutic targets in AD based on RNA sequencing (RNA-seq) analysis and experimental verification. RNA-seq was performed in the cerebral cortex and hippocampus of 5×FAD mice of AD to systematically investigate altered lncRNA-associated ceRNA regulatory network, along with qualitative analyses for key differentially expressed lncRNAs, miRNAs, and mRNAs involved. The results showed that 7 lncRNAs were significantly altered in the cortex and hippocampus of 5×FAD mice compared with WT mice. The potential functions of differentially expressed genes were highly correlated with learning and memory activities and the pathogenesis of AD. Furthermore, lncRNA Xist and highly correlated miRNAs and mRNAs were identified as key mediators of pathophysiological processes in AD. Our findings illustrated the AD-derived lncRNA-mediated ceRNA network, accompanied by aberrant expression involved in the pathological gene networks, which may contribute to understanding the pathological mechanism of AD and provide potential therapeutic targets for drug development.
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Project description:LncRNA expression profiling for liver tissues of mice fed for NFD, LSF and HSF groups Summary: An abstract of the experiment and the data analysis. Experiment Workflow: A workflow of the experiment and the data analysis. Project Description: Sample and experiment information. Array Information: Mouse 8 x 60K LncRNA expression array information. Summary Table of Files for Data Delivery: Contains summary table of files for data delivery and the recommended software programs for viewing the data. Data Analysis for LncRNAs 1. Raw LncRNA data normalization and low intensity filtering: Raw signal intensities were normalized in quantile method by GeneSpring GX v11.5.1, and low intensity LncRNAs were filtered (LncRNAs that at least 6 out of 9 samples have flags in Present or Marginal were chosen for further analysis, these LncRNAs can be found from the LncRNA Expression Profiling Data.xls file). 2. Quality assessment of LncRNA data after filtering: Contains Box Plot and Scatter Plot for LncRNAs after filtering (This data can be found from the LncRNA Expression Profiling Data.xls file). 3. Differentially expressed LncRNAs screening: Contains differentially expressed genes with statistical significance that passed Volcano Plot filtering (Fold Change >= 2.0, P-value <= 0.05) (This data can be found from the Differentially Expressed LncRNAs.xls file). 4. Heat Map and Hierarchical Clustering: Hierarchical Clustering of Differentially Expressed LncRNAs (The heat map can be found from the LncRNA Expression Profiling Data.xls file). Data Analysis for mRNAs 1. Raw mRNA data normalization and low intensity filtering: Raw signal intensities were normalized in quantile method by GeneSpring GX v11.5.1, and low intensity mRNAs were filtered (mRNAs that at least 6 out of 9 samples have flags in Present or Marginal were chosen for further analysis, these mRNAs can be found from the mRNA Expression Profiling Data.xls file). 2. Quality assessment of mRNA data after filtering: Contains Box Plot and Scatter Plot for mRNAs after filtering (This data can be found from the mRNA Expression Profiling Data.xls file). 3. Differentially expressed mRNAs screening: Contains differentially expressed genes with statistical significance that passed Volcano Plot filtering (Fold Change >= 2.0, P-value <= 0.05) (This data can be found from the Differentially Expressed mRNAs.xls file). 4. Heat Map and Hierarchical Clustering: Hierarchical Clustering of Differentially Expressed mRNAs (The heat map can be found from the mRNA Expression Profiling Data.xls file). 5. Pathway analysis: Pathway analysis of the differentially expressed mRNAs. 6. GO analysis: GO term analysis of the differentially expressed mRNAs. LncRNA Classification and Subgroup Analysis 1. Rinn lincRNAs profiling: Contains profiling data of all lincRNAs based on John Rinn's papers (This data can be found from the Rinn lincRNAs profiling.xls file). 2. LincRNAs nearby coding gene data table: Contains the differentially expressed lincRNAs and nearby coding gene pairs (distance < 300 kb) (This data can be found from the LincRNAs nearby coding gene data table.xls file). Sample RNA Quality Control: Sample quality control data file from NanoDrop ND-1000 spectrophotometer and standard denaturing agarose gel electrophoresis. Methods: A brief introduction of methods for sample preparation, microarray design, experiment, and data analysis.
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| EGAS00001003922 | EGA