Filters
Technology
Platform
Mus musculus
14 Downloadable Samples
Illumina HiSeq 2000
Description
Through the generation of humanized FUS mice expressing full length human FUS, we identify that when expressed at near endogenous murine FUS levels both wild-type or ALS- and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels/transporters essential for synaptic function, and reduced synaptic activity, without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain-of-toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive, age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs. Methods: RNA from mouse spinal cords of 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was extracted with TRIzol. RNA quality was measured using the Agilent Bioanalyzer system and processed using the Illumina TruSeq Stranded mRNA Sample Preparation Kit according to manufacturer's protocols. mRNA profiles were generated by deep sequencing, with n=3 biological replicates per group. Results: We mapped on average 15 million non-redundant reads per sample. Fastq files were aligned to mouse reference genome (mm9 UCSC Genome Browser) using TopHat workfow and the transcript abundance for each annotated protein-coding gene [as fragments per kilobase of transcript per million mapped reads (FPKM)] was estimated by Cufflinks. 13,468 genes which expressed FPKM>=1 were kept for downstream analyses. RNA profiles from normal (Non-Tg) and humanized hgFUSWT mice were almost undistinguishable. Both humanized mutant FUS lines had highly distinct RNA profiles [determined with unsupervised hierarchical clustering and principal component analysis (PCA)], with 709 down and 348 up-regulated genes relative to age-matched Non-Tg or humanized hgFUSWT littermates (P<0.05). These changes uncovered FUS mutant dependent altered pathways that may contribute to ALS/FTD-linked mutant FUS-mediated toxicity. The validation by RT-QPCR of altered expression of 20 genes is shown in Figure 5. Overall design: RNA expression profile of mouse spinal cords from 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was obtained by deep sequencing in n=3 indendepent animals per genotype using Illumina HiSeq 2000 sequencer.
Publication Title
ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
With the goal of specifically dissecting the toxicogenomic signatures of the helper-dependent (HD) human (HAd5) and canine (CAV-2) adenovirus, the VSV-G-pseudotyped SIN HIV-1 (LV) and the Adenoviral-associated vector 2/9 for human neurons (AAV2/9), we transduced a bona fide human neuronal system with HD-HAd5, HD-CAV-2, LV and AAV2/9, we analysed the transcriptional response of more than 47,000 transcripts using gene chips.
Publication Title
Differentiated neuroprogenitor cells incubated with human or canine adenovirus, or lentiviral vectors have distinct transcriptome profiles.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols.
Publication Title
Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected].
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Publication Title
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression study of DSG2 silenced human microvascular endothelial cells
Publication Title
Desmoglein-2-integrin Beta-8 interaction regulates actin assembly in endothelial cells: deregulation in systemic sclerosis.
Sample Metadata Fields
Specimen part
View Samples
GSE16558- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Specific microRNA (miRNA) signatures have been associated with different cytogenetic subtypes in acute leukemias. This finding prompted us to investigate potential associations between genetic abnormalities in multiple myeloma (MM) and singular miRNA expression profiles. Moreover, global gene expression profiling was also analyzed to find correlated miRNA-gene expression and select miRNA target genes that show such correlation. For this purpose, we analyzed the expression level of 365 miRNAs and the gene expression profiling in sixty newly diagnosed MM patients, selected to represent the most relevant recurrent genetic abnormalities. Supervised analysis showed significantly deregulated miRNAs in the different cytogenetic subtypes as compared to normal PC. Interestingly, miR-1 and miR-133a clustered on the same chromosomal loci, were specifically overexpressed in the cases with t(14;16). The analysis of the relationship between miRNA expression and their respective target genes showed a conserved inverse correlation between several miRNAs deregulated in MM cells and CCND2 expression level. These results illustrate, for the first time, that miRNA expression pattern in MM is associated with genetic abnormalities, and that the correlation of the expression profile of miRNA and their putative mRNA targets is useful to find statistically significant protein-coding genes in MM pathogenesis associated to changes in specific miRNAs.
Publication Title
Deregulation of microRNA expression in the different genetic subtypes of multiple myeloma and correlation with gene expression profiling.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 14 Downloadable Samples
- Agilent-014693 Human Genome CGH Microarray 244A (Feature number version), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of ALR-deficient cells indicates that ALRs are not required for the IFN response to intracellular DNA. To explore whether AIM2-like receptors activated another innate signaling pathway upon
Publication Title
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Sample Metadata Fields
Treatment, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gain or loss of genes and deregulation of gene expression can result in cumulative and progressive disruptions of normal cellular functions.
Publication Title
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Sample Metadata Fields
Specimen part
View Samples