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GSE3595
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
KLF7 null mice show profound axonal growth defects in the olfactory epithelium. The goal of this study was the identification of potential KLF7 target genes in olfactory sensory neurons.
Publication Title
Identification of genes regulated by transcription factor KLF7 in differentiating olfactory sensory neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
Illumina HiSeq 2000
Description
We report the application of high-throughput RNA sequencing to the human prefrontal cortex. The brain dataset was obtained by sequencing total RNAs extracted from the dorsolateral prefrontal cortex of five deceased human patients with no apparent pathology, followed by depletion of ribosomal RNA to obtain all non-rRNA coding and non-coding RNAs in the human brain transcriptome. Overall design: Five samples were sequenced, four coming from frozen brain tissue (frontal cortex) of deceased female human patients with no remarkable pathology, and one from a male patient with no remarkable pathology.
Publication Title
HAMR: high-throughput annotation of modified ribonucleotides.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
The surprising observation that virtually the entire human genome is transcribed means we know very little about the function of many emerging classes of RNAs, except their astounding diversity. Traditional RNA function prediction methods rely on sequence or alignment information, which are limited in their ability to classify classes of non-coding RNAs (ncRNAs). To address this, we developed CoRAL, a machine learning-based approach for classification of RNA molecules. CoRAL uses biologically interpretable features including fragment length, cleavage specificity, and antisense transcription to distinguish between different ncRNA classes. We evaluated CoRAL using genome-wide small RNA sequencing (smRNA-seq) datasets from two human tissue types (brain and skin [GSE31037]), and were able to classify six different types of RNA transcripts with 79~80% accuracy in cross-validation experiments, and with 71~73% accuracy when CoRAL uses one tissue type for training and the other as validation. Analysis by CoRAL revealed that long intergenic ncRNAs, small cytoplasmic RNAs, and small nuclear RNAs show more tissue specificity, while microRNAs, small nucleolar, and transposon-derived RNAs are highly discernible and consistent across the two tissue types. The ability to consistently annotate loci across tissue types demonstrates the potential of CoRAL to characterize ncRNAs using smRNA-seq data in less characterized organisms. Overall design: Four samples were sequenced, each one coming from frozen brain tissue (frontal cortex) of a deceased female human patient with no remarkable pathology.
Publication Title
HAMR: high-throughput annotation of modified ribonucleotides.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression of hepatic stellate cells exposed to fetal bovine serum (FBS)
Publication Title
Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
TAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking and RNA stability. However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates. We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (?NLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm. These mice did not exhibit a significant number of cytoplasmic aggregates, but did display a loss of endogenous mouse nuclear TDP-43 as well as dramatic changes in gene expression as measured by microarray. Here, we analyze RNA-sequencing data from the ?NLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice and High Throughput Sequencing of RNA isolated by CrossLinking ImmunoPrecipitation (HITS-CLIP) data of TDP-43’s RNA binding targets to further investigate the dysregulation of gene expression in the ?NLS model. This analysis reveals that the transcriptomic effects of the overexpression of the ?NLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function. Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing. These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains. Overall design: RNAseq of bigenic (n=4) ?NLS-hTDP-43 and control nontransgenic (n=4) mouse cortex
Publication Title
Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq1000
Description
We hypothesize that the observed differences in incidences of pleural and peritoneal malignant mesothelioma (MM) are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis, we characterized cellular responses to asbestos in a controlled environment using high-throughput RNA sequence and other assays. Overall design: Examination of asbestos-treated versus untreated mesothelial cells from four cell lines representing two tissue types in culture.
Publication Title
Differential Susceptibility of Human Pleural and Peritoneal Mesothelial Cells to Asbestos Exposure.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Interleukin (IL)-17 plays an important and protective role in host defence and has been demonstrated to orchestrate airway inflammation by cooperating with and inducing proinflammatory cytokines. Mircoarrays were used to identify immediate-early/ primary response IL-17A-dependent gene transcripts in primary human bronchial ASM cells from mild asthmatic and healthy individuals.
Publication Title
IL-17A mediates a selective gene expression profile in asthmatic human airway smooth muscle cells.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
E-cadherin downregulation in cancer cells is associated with epithelial-to-mesenchymal transition (EMT) and metastatic prowess, but the underlying mechanisms are incompletely characterized. In this study, we probed E-cadherin expression at the plasma membrane as a functional assay to identify genes involved in E-cadherin downregulation. The assay was based on the E-cadherin-dependent invasion properties of the intracellular pathogen Listeria monocytogenes. On the basis of a functional readout, automated microscopy and computer-assisted image analysis were used to screen siRNAs targeting 7,000 human genes. The validity of the screen was supported by its definion of several known regulators of E-cadherin expression, including ZEB1, HDAC1 and MMP14. We identified three new regulators (FLASH, CASP7 and PCGF1), the silencing of which was sufficient to restore high levels of E-cadherin transcription. Additionally, we identified two new regulators (FBXL5 and CAV2), the silencing of which
Publication Title
Novel strategies to enforce an epithelial phenotype in mesenchymal cells.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
We investigated the route of neurotrophic cue delivery to the nerves
Publication Title
Loss of p53 drives neuron reprogramming in head and neck cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Objective: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods: Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results: Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38 signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38 in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38-controlled transcripts comprising female- and male-specific gene modules, with greater p38 dependence of pro-inflammatory gene expression in females. Interpretation: Our findings demonstrate a key role for p38 in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS
Publication Title
Sex-specific control of central nervous system autoimmunity by p38 mitogen-activated protein kinase signaling in myeloid cells.
Sample Metadata Fields
Sex, Specimen part
View Samples