Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles.
A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.
No sample metadata fields
View SamplesTemporal changes of gene expression from 1-wk- to 4-wk and 8-wk-old mouse in heart, kidney and lung. Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified >1600 genes that were regulated with age coordinately in kidney, lung, and heart of juvenile mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly downregulated with age. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size.
An extensive genetic program occurring during postnatal growth in multiple tissues.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Subject, Time
View SamplesC57Bl/6 wild-type and STAT6 KO mice were used to study PPARg and IL-4 signaling. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and frech media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Time
View SamplesIn 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.
Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma.
Sex, Age, Specimen part
View SamplesPhotoreceptor damage in adult mammals results in permanent cell loss and glial scarring in the retina. In contrast, adult zebrafish can regenerate photoreceptors following injury. By using a stable transgenic line in which GFP is driven by the cis-regulatory sequences of a glial specific marker gfap, Tg(gfap:GFP)mi2002, previous studies showed that Mller glia, the radial glial cells in the retina, proliferate after photoreceptor loss and give rise to neuronal progenitors that eventually differentiate into regenerated photoreceptors. To identify the molecular mechanisms that initiate this regenerative response, Mller glia were isolated from Tg(gfap:GFP)mi2002 fish during the early stages of regeneration after light lesion and gene expression profiles were generated by microarray analyses.
Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish.
No sample metadata fields
View SamplesThe goal of the project was to isolate single miRNA-expressing cells labelled by GFP reporter genes under the control of endogenous miRNA promoters and analyze expression levels of miRNA target genes in these cells. GFP-positive miRNA-expressing cells and GFP-negative cells from the rest of the embryos were purified at the same developmental stage to the cellular resolution using fluorescent activated cell sorting (FACS). Focus was on regulation by miR-206 and miR-133 in the developing somites and miR-124 in the developing central nervous system. Comparison of wild-type embryos and those lacking miRNAs revealed predicted
Coherent but overlapping expression of microRNAs and their targets during vertebrate development.
No sample metadata fields
View SamplesWallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slow (WldS) mutant gene, a gene that confers axonal protection in the distal stump after injury, therefore causing significant delays in WD, neuroinflammation, and axonal regeneration.
Transcriptional profiling of the injured sciatic nerve of mice carrying the Wld(S) mutant gene: identification of genes involved in neuroprotection, neuroinflammation, and nerve regeneration.
Specimen part, Time
View SamplesAstrogliosis is a hallmark of the response to brain ischemia, comprised of changes in gene expression and morphology. Hsp72 protects from cerebral ischemia, and although several mechanisms of protection have been investigated, effects on astrocyte activation are unknown. To identify potential mechanisms of protection, gene expression was assessed in mice subjected to middle cerebral artery (MCAO) or sham surgery, of either wildtype (WT) or Hsp72-overexpressing (Hsp72Tg) mice. After stroke, both genotypes exhibited genes related to cell death, stress response, and immune response. Furthermore, genes indicative of astrocyte activation, including cytoskeletal proteins and cytokines, were upregulated. To measure astrocyte activation after stroke, detailed histological and morphological analyses were performed in the cortical penumbra after stroke using unbiased stereology. Consistent with other reports, we observed a marked and persistent increase in glial fibrillary acidic protein (GFAP ) as soon as 3 hours after MCAO. In contrast, vimentin immunoreactivity appeared 12-24 hours after stroke, peaked at 72 hours, and returned to baseline after 30 days. Surprisingly, no change in overall astrocyte number was observed based on glutamine synthetase (GS) immunoreactivity. To determine if Hsp72Tg mice exhibited altered astrocyte activation compared to WT controls, morphological evaluation by fractal analysis was used. Overexpression of Hsp72 reduced astrocyte cell area, arbor area, and to a lesser extent fractal dimension, 72 hours following stroke. In conclusion, in vivo overexpression of Hsp72 alters gene expression following stroke, including genes involved in astrocyte activation, and decreases astrocyte activation acutely following MCAO. Thus, modulation of astrogliosis may be a neuroprotective mechanism exerted by Hsp72 after ischemia.
Effects of heat shock protein 72 (Hsp72) on evolution of astrocyte activation following stroke in the mouse.
Sex, Treatment
View SamplesTgif1 is a transcriptional corepressor that limits TGF responsive gene expression. TGF signaling has antiproliferative effects in several cell types, generally resulting in a G1 arrest. Mouse embryo fibroblasts (MEFs) are primary cells with limited life-span, that senesce after several passages in culture.
Premature senescence and increased TGFβ signaling in the absence of Tgif1.
Specimen part
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