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GSE78895
Mus musculus
31 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Primary glioblastoma, representing over 90% of adult glioblastoma, develop rapidly without preexisting lower-grade glioma. We have generated a mouse model of primary glioblastoma driven by a single p53 mutation. These p53-mutant gliomas lose the syntenic region of human chromosome 10q, which is mapped to mouse chr19 and chr7. Loss of mouse chr19, containing Pten, activates PI3K/Akt signaling.
Publication Title
Opposing Tumor-Promoting and -Suppressive Functions of Rictor/mTORC2 Signaling in Adult Glioma and Pediatric SHH Medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mustela putorius furo
- 20 Downloadable Samples
- Affymetrix Canine Genome 2.0 Array (canine2)
Description
Background: Type I interferons (IFNs) are essential to the clearance of viral diseases, in part by initiating upregulation of IFN regulated genes (IRGs). A clear distinction between genes upregulated directly by virus and genes upregulated by secondary IFN production has not been made. Here we investigated the genes regulated by IFN-a2b compared to the genes regulated by SARS-CoV infection in ferrets.
Publication Title
Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
NextSeq 500, Illumina HiSeq 2000
Description
The KDM6 histone demethylases (UTX/KDM6A and JMJD3/KDM6B) mediate removal of repressive histone H3K27me3 marks to establish transcriptionally permissive chromatin. Loss of UTX in female mice is embryonic lethal. Unexpectedly, male UTX-null mice escape embryonic lethality due to expression of UTY, a paralog lacking H3K27-demethylase activity. This suggests that UTX plays an enzyme-independent role in development, and challenges the need for active H3K27-demethylation in vivo. However, the requirement for active H3K27-demethylation in stem cell-mediated tissue regeneration remains untested. Using an inducible mouse knockout that ablates UTX in satellite cells, we show that active H3K27-demethylation is necessary for muscle regeneration. Indeed, loss of UTX in satellite cells blocks myofiber regeneration in both male and female mice. Furthermore, we demonstrate that UTX mediates muscle regeneration through its H3K27-demethylase activity using a chemical inhibitor, and a demethylase-dead UTX knock-in mouse. Mechanistically, dissection of the muscle regenerative process revealed that UTX is required for expression of the transcription factor Myogenin that drives differentiation of muscle progenitors. Thus, we have identified a critical role for the enzymatic activity of UTX in activating muscle-specific gene expression during myofiber regeneration, revealing for the first time that active H3K27-demethylation has a physiological role in vivo. Overall design: Satellite cells were sorted based on Cre-dependent expression of TdT reporter gene. Sorted UTXmKO or UTX WT satellite cells were then induced to differentiate for 24 hrs. RNA was then isolated and subjected to RNA-Seq analysis.
Publication Title
UTX demethylase activity is required for satellite cell-mediated muscle regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mustela putorius furo
- 16 Downloadable Samples
- Affymetrix Canine Genome 2.0 Array (canine2)
Description
The 2009 H1N1 influenza pandemic has prompted a significant need for the development of efficient, single-dose, adjuvanted vaccines. Here we investigated the adjuvant potential of CpG oligodeoxynucleotide (ODN) when used with a human seasonal influenza virus vaccine in ferrets. We found that the CpG ODNadjuvanted vaccine effectively increased antibody production and activated type I interferon (IFN) responses compared to vaccine alone. Based on these findings, pegylated IFN- 2b (PEG-IFN) was also evaluated as an adjuvant in comparison to CpG ODN and complete Freunds adjuvant (CFA). Our results showed that all three vaccines with adjuvant added prevented seasonal human A/Brisbane/59/2007 (H1N1) virus replication more effectively than did vaccine alone. Gene expression profiles indicated that, as well as upregulating IFN-stimulated genes (ISGs), CpG ODN enhanced B-cell activation and increased Toll-like receptor 4 (TLR4) and IFN regulatory factor 4 (IRF4) expression, whereas PEG-IFN augmented adaptive immunity by inducing major histocompatibility complex (MHC) transcription and Ras signaling. In contrast, the use of CFA as an adjuvant induced limited ISG expression but increased the transcription of MHC, cell adhesion molecules, and B-cell activation markers. Taken together, our results better characterize the specific molecular pathways leading to adjuvant activity in different adjuvant-mediated influenza virus vaccinations.
Publication Title
Molecular characterization of in vivo adjuvant activity in ferrets vaccinated against influenza virus.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed whole transcriptome profiling on sorted tissue macrophages from the spleen or from visceral adipose tissue (VAT) of wild-type mice that are 3-month or 24-month of age or from 24-month Nlrp3-/- mice Overall design: Profiles were generated on fluorescence-activated-cells (FACs) sorted F480+CD11b+ cells from spleen or adipose tissue, using sequencing analysis
Publication Title
Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mustela putorius furo
- 28 Downloadable Samples
- Affymetrix Canine Genome 2.0 Array (canine2)
Description
Background: Pandemic H1N1 influenza A is a newly emerging strain of human influenza that is easily transmitted between people and has spread globally to over 116 countries. Human infection leads to symptoms ranging from mild to severe with lower respiratory complications observed in a small but significant number of infected individuals. Little is currently known about host immunity and Pandemic H1N1 influenza infections.
Publication Title
Modeling host responses in ferrets during A/California/07/2009 influenza infection.
Sample Metadata Fields
Specimen part
View Samples- Mustela putorius furo
- 23 Downloadable Samples
- Affymetrix Canine Genome 2.0 Array (canine2)
Description
A global genomics approach was used to identify patterns of immune dysregulation during H5N1 influenza virus infection as the host response, in particular hyperchemokinemia, is thought to contribute to the extreme pathology associated with this disease.
Publication Title
Gene expression analysis of host innate immune responses during Lethal H5N1 infection in ferrets.
Sample Metadata Fields
Specimen part
View Samples- Mustela putorius furo
- 37 Downloadable Samples
- Affymetrix Canine Genome 2.0 Array (canine2)
Description
To further investigate the underlying mechanisms of severe acute respiratory syndrome (SARS) pathogenesis and evaluate the therapeutic efficacy of potential drugs and vaccines it is necessary to use an animal model that is highly representative of the human condition in terms of respiratory anatomy, physiology and clinical sequelae. The ferret, Mustela putorius furo, supports SARS-CoV replication and displays many of the symptoms and pathological features seen in SARS-CoV-infected humans. We have recently established a SARS-CoV infection-challenge ferret platform for use in evaluating potential therapeutics to treat SARS. The main objective of the current study was to extend our previous results and identify early host immune responses upon infection and determine immune correlates of protection upon challenge with SARS-CoV in ferrets.
Publication Title
Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 2 Downloadable Samples
- IlluminaHiSeq2500
Description
A zebrafish forward genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in the lysosomal hydrolase Cathepsin L that manifests the hallmarks of human lysosomal storage diseases. In uninfected mutants, macrophages progressively accumulate undigested material in their lysosomes, leading to impaired migration and the accumulation of unengulfed cell debris. During mycobacterial infection, these vacuolated macrophages cannot migrate to phagocytose infected macrophages undergoing apoptosis in the tuberculous granuloma. Consequently, unengulfed apoptotic macrophages undergo secondary necrosis causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal accumulations similarly impair migration to newly infecting mycobacteria. We find that important aspects of this phenotype are recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of alveolar macrophages from smokers exhibit lysosomal accumulations and do not migrate to Mycobacterium tuberculosis. This incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis. Overall design: A forward genetic screen for zebrafish larvae that are hypersusceptible to Mycobacterium marinum infection identified a mutation in the transcription factor snapc1b at 13: 37996163 (T->C). Individuals of wild type (T/T) and mutant (C/C) were genotyped and pooled respectively for RNA isolation and transcriptome analysis.
Publication Title
Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- NextSeq 500
Description
ROR?t is well recognized as the lineage defining transcription factor for TH17 cell development. However, the cell-intrinsic mechanisms that negatively regulate TH17 cell development and autoimmunity remain poorly understood. Here we demonstrate that the transcriptional repressor REV-ERBa is exclusively expressed in TH17 cells, competes with ROR?t for their shared DNA consensus sequence, and negatively regulates TH17 cell development via repression of genes traditionally characterized as ROR?t-dependent, including Il17a. Deletion of REV-ERBa enhanced TH17-mediated pro-inflammatory cytokine expression, exacerbating experimental autoimmune encephalomyelitis (EAE) and colitis. Treatment with REV-ERB-specific synthetic ligands, which have similar phenotypic properties as ROR? modulators, suppressed TH17 cell development, was effective in colitis intervention studies, and significantly decreased the onset, severity, and relapse rate in several models of EAE without affecting thymic cellularity. Our results establish that REV-ERBa negatively regulates pro-inflammatory TH17 responses in vivo and identifies the REV-ERBs as potential targets for the treatment of TH17-mediated autoimmune diseases. Overall design: 10 samples; 5 conditions with 2 replicates per condition
Publication Title
REV-ERBα Regulates T<sub>H</sub>17 Cell Development and Autoimmunity.
Sample Metadata Fields
Specimen part, Subject
View Samples