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SRP113494
Mus musculus
142 Downloadable Samples
Illumina HiSeq 4000, Illumina HiSeq 2500
Description
Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX), however the differentially translating mRNAs that contribute to altered neural function are not known. We used Translating Ribosome Affinity Purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1-/y) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded. Surprisingly, enhancement rather than inhibition of M4 activity normalizes core phenotypes in the Fmr1-/y, including excessive protein synthesis, exaggerated mGluR-LTD, and audiogenic seizures. These results suggest that not all excessively translated mRNAs in the Fmr1-/y brain are detrimental, and some may be candidates for enhancement to correct pathological changes in the FX brain. Overall design: 6 biological replicates of total hippocampal mRNA (Input) from WT and Fmr1 KO littermate pairs and CA1-TRAP-IP (IP) from the same 6 WT and KO littermate pairs.
Publication Title
Cell-Type-Specific Translation Profiling Reveals a Novel Strategy for Treating Fragile X Syndrome.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2000
Description
Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies. Overall design: Primary analysis: 8 KD coronary arteries versus 7 childhood control coronary arteries. Subanalysis 1: 4 untreated KD coronary arteries versus 7 childhood control coronary arteries and subanalysis 2: 4 treated KD coronary arteries versus 7 childhood control coronary arteries
Publication Title
The transcriptional profile of coronary arteritis in Kawasaki disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 34 Downloadable Samples
Illumina humanRef-8 v2.0 expression beadchip
Description
Here we present a strategy to adapt hESCs to high-throughput screening (HTS) conditions, resulting in an assay suitable for the discovery of small molecules that drive hESC self-renewal or differentiation. Use of this new assay has led to the identification of several currently marketed drugs and natural compounds promoting short-term hESC maintenance and compounds directing early lineage choice. Global gene expression analysis upon drug treatment reveals overlapping and novel pathways correlated to hESC self-renewal and differentiation. Our results demonstrate feasibility of hESC-based HTS and enhance the available repertoire of chemical compounds for manipulating hESC fate.
Publication Title
High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina HiSeq 2000
Description
The goal of the study was to analyze the principles governing the usage of alternatively spliced transcript isoform of four types of T-cells (Naïve, Central Memory, Transitional Memory and Effector Memory) between resting and activated status. However, the principles discovered in the T cells were universal and can also be applied to other cell type and tissues. Overall design: Four types of T cells were sorted and whole transcriptome analysis was performed using an Illumina machine The readme.txt contains the column headers and description for the processed data files.
Publication Title
Stochastic principles governing alternative splicing of RNA.
Sample Metadata Fields
Subject
View Samples- Macaca mulatta
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates.
Publication Title
Gene expression in primate liver during viral hemorrhagic fever.
Sample Metadata Fields
Specimen part, Time
View Samples- Zea mays
- 9 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Anthocyanin induction in plant is considered a general defense response against biotic and abiotic stresses. The infection by Ustilago maydis, the corn smut pathogen, is accompanied with anthocyanin induction in leaf tissue. We revealed that anthocyanin is intentionally induced by the virulence promoting secreted effector protein Tin2. Tin2 protein functions inside plant cells where it interacts with cytoplasmic maize protein kinase ZmTTK1. Tin2 masks an ubiquitin-proteasome degradation motif in ZmTTK1 leading to a more stable active kinase. Active ZmTTK1 controls transcriptional activation of genes in the anthocyanin biosynthesis pathway rerouting phenylalanine away from lignin biosynthesis.
Publication Title
A secreted Ustilago maydis effector promotes virulence by targeting anthocyanin biosynthesis in maize.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of Early Myogenesis Reveals an Extensive Set of Transcriptional Regulators Whose Knock-down Can Inhibit Differentiation
Publication Title
Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAs were isolated from FACS sorted ScxGFP positive cells of hindlimbs at E11.5, E13.5 and E15.5, and characterized by RNAseq Overall design: 18 hindlimbs, 12 hindlimbs and 11 hindlimbs were pooled together for E11.5, E13.5 and E15.5, respectively.GFP positive cells were FACS sorted, then for RNA extraction, cDNA library preparation and proceeded for RNAseq
Publication Title
Whole transcriptome expression profiling of mouse limb tendon development by using RNA-seq.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAs were isolated from FACS sorted ScxGFP positive cells and GFP negative cells of forelimbs at E13.5, and characterized by RNAseq Overall design: for each sample, 3 pairs of total 6 E13.5 forelimbs were pooled together, both GFP positive cells and GFP negative cells were FACS sorted, then for RNA extraction, cDNA library preparation and proceeded for RNAseq
Publication Title
Whole transcriptome expression profiling of mouse limb tendon development by using RNA-seq.
Sample Metadata Fields
No sample metadata fields
View Samples