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GSE27309
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
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 15 Downloadable Samples
Description
The Runx genes are important in development and cancer, where they can act either as oncogenes or tumour supressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins reflecting the marked effects of Runx on cell adhesion.
Publication Title
Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
29-32 days old male mice where either treated with Phenobarbital or untreated
Publication Title
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Ingestion of collagen peptide elicits beneficial effects on the body. Improvement of blood lipid is one of the effects, but its mechanism remains unclear. Male BALB/cCrSlc mice were bred with the AIN-93M diet containing 14% casein or AIN-93M-based low-protein diet containing 10% casein or diet containing 6% casein+4% collagen peptide (n=12/group) for 10 weeksTotal, free, and esterified cholesterol levels in the blood decreased in the collagen peptide group. DNA microarray analysis of the liver revealed that expression of the genes related to lipid metabolic process, such as PPAR signaling pathway and fatty acid metabolism, increased in the collagen peptide group compared to the 10% casein group. In contrast, expression of the genes related to unfolded protein response (UPR) and protein level of phospho-IRE1 decreased. Our data suggest that lipid metabolism in the liver was altered by collagen ingestion, which probably results in the decreased levels of blood cholesterol.
Publication Title
Collagen peptide ingestion alters lipid metabolism-related gene expression and the unfolded protein response in mouse liver.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Background: It is recognized that atherosclerosis can regresses at least in animal models. However, little is known about the mechanisms. We induced regression of advanced atherosclerosis in apolipoprotein E deficient (APOE/) mice and studied underlying mechanisms. Unexpectedly, our study led to the role of interleukin-7 (IL-7) in atherogenesis.
Publication Title
Interleukin-7 induces recruitment of monocytes/macrophages to endothelium.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Primordial genomic challenge compromises embryonic development and survival, and surveillance of deployed transcriptional programs may provide an early opportunity to forecast phenotype abnormalities. Here, comparisons between wild-type and calreticulin-ablated embryonic stem cells revealed transcriptome shifts precipitated by calreticulin loss. Bioinformatic analysis identified down and up-regulation in 1187 and 418 genes, respectively. Cardiovascular development precedes other organogenic programs, and examination of cardiogenic genes revealed a map of calreticulin-calibrated expression profiles that encompass the developmental regulators, Ccnd1, Ccnd2 and Notch1. Interrogation of primary function in the resolved network forecasted abnormalities during myocardial development. Whole embryo magnetic resonance imaging, verified by pathoanatomical analysis, diagnosed prominent ventricular septal defect. Correlation clustering and network resolution of probesets associated with protein folding/chaperoning and calcium handling demonstrated 14 and 19 genes, respectively, modulated by calreticulin deficiency. Calreticulin deletion provoked ontological re-prioritization of gene expression, molecular transport and protein trafficking that translated into multiple subcellular functional outcomes. Individual stem cell-derived cardiomyocytes lacking calreticulin demonstrated a disorganized contractile apparatus with mitochondrial paucity and architectural aberrations. Thus, bioinformatic deconvolution of primordial embryonic stem cell transcriptomes enables predictive phenotyping of defective developmental networks that coalesce from complex systems biology hierarchies.
Publication Title
Decoded calreticulin-deficient embryonic stem cell transcriptome resolves latent cardiophenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules.
Publication Title
The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
Description
Aim of present study was to describe the changes induced deletion of the Wfs1 gene in the temporal lobe of mice. Mutant mice were backcrossed to two different genomic backgrounds in order to exclude confounding foreign genomic background influence. Samples from temporal lobes were analyzed by using Affymetrix Genechips, expression profiles were functionally annotated by using GSEA and Ingenuity Pathway Analysis. We found that Wfs1 mutant mice are significantly smaller (20.9 1.6 g) than their wild-type counterparts (31.0 0.6g, p < 0.0001). Interestingly, genechip analysis identified growth hormone transcripts up-regulated and functional analysis found appropriate pathways activated. Moreover, we found significant increase in the level of IGF1 in the plasma of wfs1 mutant mice. Taken together, wfs1 mutation induces growth retardation whereas the growth hormone pathway is activated. Further studies are needed to describe biochemical and molecular details of the growth hormone axis in the wfs1 mutant mice.
Publication Title
Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Understanding the response of memory CD8 T cells to persistent antigen re-stimulation and the role of CD4 T cell help is critical to the design of successful vaccines for chronic diseases. However, studies comparing the protective abilities and qualities of memory and nave cells have been mostly performed in acute infections, and little is known about their roles during chronic infections. Herein, we show that memory cells dominate over nave cells and are protective when present in large enough numbers to quickly reduce infection. In contrast, when infection is not rapidly reduced, memory cells are quickly lost, unlike nave cells. This loss of memory cells is due to (i) an early block in cell proliferation, (ii) selective regulation by the inhibitory receptor 2B4, and (iii) increased reliance on CD4 T cell help. These findings have important implications towards the design of T cell vaccines against chronic infections and tumors.
Publication Title
Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load.
Sample Metadata Fields
Specimen part
View Samples