Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE85294 | GEO | 2017/06/11
SECONDARY ACCESSION(S): PRJNA338118
REPOSITORIES: GEO
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2013-08-05 | E-GEOD-47494 | biostudies-arrayexpress
Project description:Long-noncoding RNA (lncRNA) comprise a new class of genes that have been assigned key roles in development and disease. Many lncRNAs are specifically transcribed in the brain where they regulate the expression of protein-coding genes that underpin neuronal function; however, their role in learning and memory remains largely unexplored. We used RNA Capture-Seq to identify a large population of lncRNAs that are expressed in the infralimbic cortex of adult male mice in response to fear-related learning, with 14.5% of these annotated in the GENCODE database as lncRNAs with no known function. We combined these data with cell-type-specific ATAC-seq on neurons that had been selectively activated by fear-extinction learning, and discovered 434 lncRNAs derived from enhancer regions in the vicinity of protein-coding genes. We found a novel experience-induced lncRNA called ADRAM that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate early gene Nr4a2. This leads to the expulsion of histone deactylases 3 and 4, and the recruitment of the histone acetyltransferase creb binding protein, which drives learning-induced Nr4a2 expression. Knockdown of ADRAM disrupts this interaction, blocks the expression of Nr4a2, and ultimately impairs the formation of fear-extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain, highlights enhancer-derived RNAs (eRNAs) as key players in the epigenetic regulation of gene expression associated with fear extinction, and suggests eRNAs, such as ADRAM, may constitute viable targets in developing novel treatments for fear-related anxiety disorders.
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2012-04-28 | E-GEOD-33092 | biostudies-arrayexpress
Project description:Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. RNA CaptureSeq was perfomed on RNA extracted from adult mouse subventricular zone to better characterize rare lncRNA isoforms. Genomic regions used to design capture array are included in the raw file target_regions.bed.
2013-04-11 | E-GEOD-45277 | biostudies-arrayexpress
Project description:Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. CHIP-seq was performed on SVZ-derived neurospheres to determine the chromatin state of lncRNA promoters in adult neural stem cells
2013-04-11 | E-GEOD-45279 | biostudies-arrayexpress
Project description:Background & Aims: Inflammatory bowel diseases (IBD) are clinically manifested as ulcerative colitis (UC) and Crohn’s Disease (CD). Novel high throughput technologies revealed new categories of genes, including the long non-coding RNAs (lncRNAs), which have been involved in the pathogenesis of different human diseases; however the role and function of lncRNAs in the UC pathogenesis has not been evaluated. Methods: The gene expression patterns for both non-coding (lncRNAs) and coding (mRNA) transcripts were profiled in UC (n=8) and control (n=7) patients by ArrayStar assays. The differentially expressed genes were used to develop lncRNA signatures in UC samples. Ingenuity Software Analysis (IPA) program was used to identify the up-stream regulators of IFNG-AS1. Jurkat T cells were activated by PMA/ionomycin and IFNG and TNF protein levels were assessed by ELISA assay. Two anti-sense molecules were designed and used to block IFNG-AS1 expression levels. Colonic tissues from TNBS-treated and IL10-/- mice were used to extract RNA and examine INFG-AS1 expression by real-time PCR. Results: A unique set of lncRNAs was found to be differentially expressed between UC (n=15) and control samples (n=16). Of these, IFNG-AS1 was among the highest statistically significant lncRNAs (fold change: 5.27, p-value: 7.07E-06). Bioinformatic analyses showed that IFNG-AS1 was associated with the IBD susceptibility loci SNP rs7134599 and its genomic location is adjacent to the inflammatory cytokine, interferon-gamma (IFNG). Using the TNBS and IL10-/- mouse models of colitis, we found increased colonic expression of this lncRNA during active colitis. Utilizing the Jurkat T cell model system, we explored the mechanisms of action and found that IFNG-AS1 can positively regulate IFNG expression. Conclusions: Novel lncRNA signatures were identified to differentiate UC patients with active disease, in remission and control subjects. A subset of these lncRNAs was found to be associated with the clinically validated IBD susceptibility loci. IFNG-AS1 was one of these differentially expressed lncRNAs in UC patients and was found to regulate the key inflammatory cytokine, IFNG, in CD4 T cells. Taken together, our study revealed novel lncRNA signatures deregulated in ulcerative colitis and identified IFNG-AS1 as a novel regulator of IFNG inflammatory responses, suggesting the potential importance of non-coding RNA mechanisms on regulation of IBD-related inflammatory responses.
2016-11-08 | GSE77013 | GEO
Project description:Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. SVZ monolayer cultures were differentiated in vitro for 1,2,4 days, and gene expression changes were measured. SVZ lineage was isolated by FACS using established protocols to separate transit amplifying (TA), neuroblast (NB), activated stem cells (NSCs), and niche astrocytes (astros), and gene expression of each cell type was measured. All arrays are custom lncRNA arrays.
2013-04-11 | E-GEOD-45281 | biostudies-arrayexpress
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Project description:Long noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules that are involved in many aspects of brain function. Emerging evidence indicates that lncRNAs are localized to the synapse; however, a direct role for their activity in this subcellular compartment in memory formation has yet to be demonstrated. Using lncRNA capture-seq, we identified a Gas5 variant that accumulate in the synaptic compartment within the infralimbic prefrontal cortex of adult male C57/Bl6 mice. Gas5 RNA immunoprecipitation followed by mass spectrometry revealed that this Gas5 isoform, in association with the RNA binding proteins G3BP2 and CAPRIN1, regulates the activity-dependent trafficking and clustering of RNA granules. In addition, we found that cell-type-specific, activity-dependent, and synapse-specific knockdown of this Gas5 variant led to impaired fear extinction memory. These findings identify a new mechanism of fear extinction that involves the dynamic interaction between local lncRNA activity and RNA condensates in the synaptic compartment.
2023-11-20 | PXD046479 | Pride