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GSE8162
Mus musculus
39 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice.
Publication Title
Remodeling the cardiac transcriptional landscape with diet.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We established the transcriptional profile of brain aging and examine the global effects of vitamin E supplementation on age-related alterations in expression in the aged mouse brain.
Publication Title
Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 20 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
To investigate the global effects of vitamin E supplementation on heart aging, we used high-density oligonucleotide arrays to measure transcriptional alterations in 30-month-old B6C3F1 mice supplemented with - and -tocopherol since middle age (15 months).
Publication Title
Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study is to find the cellular and molecular mechanisms by which a naturally-occurring Np53 isoform causes accelerated aging in humans. The biological function of Np53, which lacks only 40 N-terminal amino acids, represents an example of p53 as a regulator of mammalian aging. When expressed together with WTp53 in mice, Np53 causes an aging phenotype such as shorter life span, reduced body mass, organ atrophy and osteoporosis. Because p53 must form a tetramer to regulate transcription, we generated p53 clones (based upon the structure of the native p53 tetramer) containing one Np53 linked with one WTp53 to form a functional Np53:WTp53 tetramer with 1:1 stoichiometry. Thus, our strategy ensured each p53 tetramer contained 2 Np53 and 2 WTp53 proteins. Importantly, Np53:WTp53 form stable tetramers, based upon gel filtration chromatography and structural analysis using electron microscopy. Furthermore, the Np53:WTp53 tetramer activates transcription equally well compared with WTp53 tetramers in an in vitro reconstituted transcription system. Having verified the stoichiometry, stability, structure, and activity of these Np53:WTp53 tetramers, here we used microarray analysis to compare global gene expression patterns in p53-null H1299 cells expressing either WTp53 or Np53:WTp53. As expected, global gene expression was largely similar, since the differences between Np53:WTp53 tetramers and WTp53 tetramers are slight: only 2 of 4 p53 proteins will be different in the Np53:WTp53 tetramer. Among only several dozen genes that were selectively up- or down-regulated 2-fold or greater, many genes known to regulate mammalian aging were altered in cells expressing Np53:WTp53, including insulin signaling pathway members (IRS1, INPP5D, PLK3, MAP3K1, FGF5) and regulators of glucose metabolism (SLC2A2, CRYAB, LRCH1). Expression of other key metabolic genes were also altered in cells expressing Np53:WTp53 tetramers, suggesting that global me tabolic changes might contribute to Np53:WTp53 pathology. In collaboration with Metabolon (Durham, NC), we identified approximately one hundred metabolites that were significantly up- or down-regulated in H1299 cells expressing Np53:WTp53. The metabolome analysis was a powerful complement to the gene expression data, and further suggested that the mTOR pathway (e.g. across-the-board up-regulation of amino acid levels) and mitochondrial function (e.g. up-regulation of carnitine, important for a-oxidation of fatty acids) was altered in cells expressing Np53:WTp53. These findings were subsequently validated using biochemical and cell-based approaches. Furthermore, whereas equal expression of Np53 and WTp53 cause accelerated aging in mammals, due to alternative splicing and translation initiation Np53 is a naturally-occurring isoform whose expression levels can change throughout the lifetime. Thus, the cellular and molecular mechanisms identified from this work will likely reflect changes common to normal, physiological aging.
Publication Title
The human ΔNp53 isoform triggers metabolic and gene expression changes that activate mTOR and alter mitochondrial function.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 11 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Oxidative stress may play a role in normal aging. SKN-1 is a transcription factor necessary for intestine development in Caenorhabditis elegans, which also regulates the response to oxidative stress post-embryonically. Using DNA microarrays, we found that oxidative stress induces the antioxidant response, the heat shock response, and detoxification genes, while the expression of genes involved in homeostasis, development, and reproduction were decreased. Both up-regulated and down-regulated genes can be wholly, partially, or not at all dependent on SKN-1 action. However, induction of the heat shock response by oxidative stress was not affected by SKN-1 removal.
Publication Title
Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet.
Publication Title
Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To define the contribution of p53 versus DNp63a to gene expression control, we performed a series of microarray assays for cells where p53 was activated using Nutlin-3 or DNp63a was knocked down using a stably transduced tetracycline inducible shRNA.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Increasing evidence suggests that microRNAs may play important roles in regulating self-renewal and differentiation in mammalian stem cells (SCs). Here, we explore this issue in skin. We first characterize microRNA expression profiles of skin SCs versus their committed proliferative progenies and identify a microRNA subset associating with stemness. Of these, miR-125b is dramatically downregulated in early SC-progeny. We engineer an inducible mice system and show that when miR-125b is sustained in SC-progenies, tissue balance is reversibly skewed towards stemness at the expense of epidermal, oil-gland and HF differentiation. Using gain-and-loss of function in vitro, we further implicate miR-125b as a repressor of SC differentiation. In vivo, transcripts repressed upon miR-125b induction are enriched >700% for predicted miR-125b targets normally downregulated upon SC-lineage commitment. We verify some of these miR-125b targets, and show that Blimp1 and VDR in particular can account for many tissue imbalances we see when miR-125b is deregulated.
Publication Title
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples