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Mus musculus
6 Downloadable Samples
Description
Dent disease has multiple defects attributed to proximal tubule malfunction including low molecular weight proteinuria, aminoaciduria, phosphaturia and glycosuria. In order to understand the changes in kidney function of the Clc5 transporter gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal tubules of mouse kidneys.
Publication Title
Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney.
Sample Metadata Fields
No sample metadata fields
View Samples- 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
GSE57801- Mus musculus, Drosophila melanogaster
- 35 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
Description
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We compared gene expression differences in Lyl-1 knockout vs wildtype LMPPs
Publication Title
The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
Description
Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation and reactive oxygen species scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1a is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1a activity. To test this model for the first time, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1a (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1a is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy demonstrated that PGC-1a is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1a is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1a nor mitochondrial biogenesis in skeletal muscle are required for the metabolic benefits of CR.
Publication Title
Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Description
TERT is an essential protein component of telomerase, a ribonuclearprotein complex that protects chromosomal ends. Ectopic expression of TERT in mouse skin activates hair follicle stem cells and induces active growth phase of hair cycles, called anagen. This activity of TERT is independent of its reverse transcriptase function, indicating that this is a non-telomeric function of TERT.
Publication Title
TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates and redox potential required for the generation of biomass. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. SIRT3 loss promotes a metabolic profile consistent with high glycolysis required for anabolic processes in vivo and in vitro. Mechanistically, SIRT3 mediates metabolic reprogramming independently of mitochondrial oxidative metabolism and through HIF1a, a transcription factor that controls expression of key glycolytic enzymes. SIRT3 loss increases reactive oxygen species production, resulting in enhanced HIF1a stabilization. Strikingly, SIRT3 is deleted in 40% of human breast cancers, and its loss correlates with the upregulation of HIF1a target genes. Finally, we find that SIRT3 overexpression directly represses the Warburg effect in breast cancer cells. In sum, we identify SIRT3 as a regulator of HIF1a and a suppressor of the Warburg effect.
Publication Title
SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Astrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring in vitro neural stem cell properties. In order to identify novel regulators of this astrocyte subset, we performed a genome-wide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the adult mouse cerebral cortex. The expression pattern was compared with astrocytes from normal cortex and adult neural stem cells isolated from the sub-ependymal zone (GSE18765). These comparisons revealed a set of genes up-regulated both in neurogenic neural stem cells and reactive astrocytes, including the lectins Galectin-1 and -3. These results, as well as the pattern of Galectin expression in the lesioned brain, led us to examine the functional significance of these lectins in brains of Galectin-1/3 double-knockout mice.
Publication Title
Astrocyte reactivity after brain injury-: The role of galectins 1 and 3.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 5 Downloadable Samples
Description
We investigated the role of mTORC1 in murine hematopoiesis by conditionally deleting the Raptor gene in murine hematopoietic stem cells. We observed mutliple alterations evoked by Raptor loss in hematopoiesis and profiled gene-expression alterations induced by raptor loss in Flt3-Lin-Sca1+cKit+ hematopoietic stem and progenitor enriched cell populations, 5 weeks post Raptor deletion.
Publication Title
mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis.
Sample Metadata Fields
Specimen part
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