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GSE26299
Mus musculus
107 Downloadable Samples
Description
In this study that was specifically designed to identify early stages of glaucoma in DBA/2J mice, we used genome-wide expression profiling and a series of computational methods. Our methods successfully subdivided eyes with no detectable glaucoma by conventional assays into molecularly defined stages of disease. These stages represent a temporally ordered sequence of glaucoma states. Using an array of tools, we then determined networks and biological processes that are altered at these early stages. Our strategy proved very sensitive, suggesting that similar approaches will be valuable for uncovering early processes in other complex, later-onset diseases. Early changes included upregulation of both the complement cascade and endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in the complement component 1a gene (C1qa) were robustly protected from glaucoma with the protection being among the greatest reported. Similarly, inhibition of the endothelin system was strongly protective. Since EDN2 is potently vasoconstrictive and was produced by microglial/macrophages, our data provide a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early events such as the upregulation of the complement and endothelin pathways may provide effective new treatments for human glaucoma.
Publication Title
Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
CD8 T cells play a crucial role in immunity to infection and cancer. They are maintained in constant numbers, but upon stimulation with antigen undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific populations, followed by the persistence of long-lived memory cells. Although this predictable pattern of a CD8 T cell response is well established, the underlying cellular mechanisms regulating the transition to memory remain undefined. Here we show that TRAF6, an adapter protein in the TNF-receptor (TNFR) and IL-1R/TLR superfamily, regulates CD8 T cell memory development following infection by modulating fatty acid metabolism. We show that mice with a T cell-specific deletion of TRAF6 mount robust primary CD8 T cell effector responses, but have a profound defect in their ability to generate memory. This defect is CD8 T cell intrinsic and is characterized by the disappearance of antigen-specific cells in the weeks following primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells from early timepoints following immunization exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 are unable to upregulate mitochondrial -oxidation in response to growth factor withdrawal in vitro. Treatment with drugs that induce fatty acid oxidation enabled CD8 T cell memory generation in the absence of TRAF6. Remarkably, these treatments also increased CD8 T cell memory in wild type mice, and consequently were able to significantly improve the efficacy of an experimental anti-cancer vaccine.
Publication Title
Enhancing CD8 T-cell memory by modulating fatty acid metabolism.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The human cytomegalovirus (HCMV) encodes the chemokine receptor US28 that exhibits constitutive activity. NIH-3T3 cells stably transfected with US28 present a pro-angiogenic and transformed phenotype both in vitro and in vivo.
Publication Title
The human cytomegalovirus-encoded chemokine receptor US28 promotes angiogenesis and tumor formation via cyclooxygenase-2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 42 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from normal tissues
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from normal tissues
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Description
F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from normal tissues
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
New insulin-producing pancreatic beta-cells are formed primarily by self-replication during adult life. To identify small molecules that can induce beta cell replication, a large chemical library was screened for proliferation of growth-arrested, reversibly immortalized mouse beta-cells using an automated high-throughput screening platform. A number of structurally diverse, active compounds were identified including phorbol esters, which likely act through protein kinase C, and a group of thiophene-pyrimidines that stimulate beta-cell proliferation by activating the Wnt signaling pathway. A group of dihydropyridine (DHP) derivatives was also shown to reversibly induce beta-cell replication in vitro by activating L-type calcium channels (LTCCs). Our data indicate that the LTCC agonist 2a affects the expression of genes involved in cell cycle progression and cellular proliferation. Furthermore, treatment of beta-cells with both LTCC agonist 2a and the Glp-1 receptor agonist Ex-4 showed an additive effect on beta-cell replication. The identification of small molecules that induce beta-cell proliferation suggests that it may be possible to reversibly expand other quiescent cells to overcome deficits associated with degenerative and/or autoimmune diseases.
Publication Title
Identification of small-molecule inducers of pancreatic beta-cell expansion.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
POU4F1 is associated with t(8;21) acute myeloid leukemia (AML) and contributes directly to its unique transcriptional signature
Publication Title
POU4F1 is associated with t(8;21) acute myeloid leukemia and contributes directly to its unique transcriptional signature.
Sample Metadata Fields
Specimen part
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