The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. To identify alternate regeneration pathways in the thymus, we performed an unbiased transcriptome analysis of the non-hematopoietic (CD45-) stromal cell compartment of the thymus, which is less sensitive to thymic damage compared to the CD45+ hematopoietic compartment.
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration.
Sex, Specimen part
View SamplesWe propose a method to compare the location and variability of gene ex-pression between two groups of microarrays using a permutation test based on the pairwise distance between microarrays. The microarrays could be samples from distinct clinical or biological populations or microarrays prepared at two different levels of an experimental factor. For these tests the entire microarray or some pre-specifed subset of genes, not the individual gene, is the unit of analysis. We apply this method to compare results from two dfferent protocols for preparing labeled targets for microarray hybridization and their subsequent gene expression analysis.
Assessing statistical significance in microarray experiments using the distance between microarrays.
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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 SamplesG protein-coupled receptor kinase 2 (GRK2) has emerged as a key regulator of cardiac function and myocardial structure. Cardiac GRK2 is increased in heart failure and ischemia in humans, whereas genetic inhibition of GRK2 is cardioprotective in animal models of these pathologies. However, the mechanistic basis underlying these effects are not fully understood. We have used adult GRK2 hemizygous mice (GRK2+/-) as a model to assess the effects of a sustained systemic inhibition of GRK2 in heart tissue with age.
Downregulation of G protein-coupled receptor kinase 2 levels enhances cardiac insulin sensitivity and switches on cardioprotective gene expression patterns.
Specimen part
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