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E-MEXP-1467
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Effect of FGF2 on the transcriptional profile of microvascular endothelial cells
Publication Title
A pro-inflammatory signature mediates FGF2-induced angiogenesis.
Sample Metadata Fields
Specimen part, Cell line, Compound
View Samples- Mus musculus
- 134 Downloadable Samples
Illumina HiSeq 2500
Description
Profound changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract. In contrast, stochastic loss of FoxA1/2 expression in NKX2-1-negative tumors is associated with keratinizing squamous differentiation. Using sequential in vivo recombination, we find that FoxA1/2 loss in established KRAS-driven neoplasia is sufficient for direct induction of keratinizing squamous cell carcinomas in the lung. Thus, NKX2-1, FoxA1 and FoxA2 coordinately regulate the growth and identity of lung adenocarcinoma in a context-specific manner. Overall design: Murine lung tumor cells of differing genotypes were isolated by FACS and subjected to single cell analysis using the Fluidigm C1 platform.
Publication Title
FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Triple-negative (TN) breast cancers need to be refined in order to identify therapeutic subgroups of patients.
Publication Title
Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Profound changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract. In contrast, stochastic loss of FoxA1/2 expression in NKX2-1-negative tumors is associated with keratinizing squamous differentiation. Using sequential in vivo recombination, we find that FoxA1/2 loss in established KRAS-driven neoplasia is sufficient for direct induction of keratinizing squamous cell carcinomas in the lung. Thus, NKX2-1, FoxA1 and FoxA2 coordinately regulate the growth and identity of lung adenocarcinoma in a context-specific manner. Overall design: Murine lung tumor cells of differing genotypes were isolated by FACS and subjected to total RNA-Seq.
Publication Title
FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
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- 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- 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
- 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- 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