Gene expression profiles generated from skeletal muscle biopsies taken from participants of the HERITAGE family study. Participants completed an endurance training regime in which a skeletal muscle biopsy was taken prior to the start and after the final session of the program. Biopsies were used to generate Affymetrix gene expression microarrays.
The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks.
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Specimen part
View SamplesPericonceptual supplementation of women with folate is considered a great success for public health. Higher folate status, either by supplementation, or via the mandatory fortification of grain products in the United States, has lead to significant reduction in the incidence of neural tube defects. Besides birth defects, folate deficiency has been linked to a variety of morbidities, most notably to increased risk for cancer. However, recent evidence suggests that excess folate may be detrimental - for birth defect incidence or in the progression of cancer. How folate mediates beneficial or detrimental effects is not well understood. It is also unknown what molecular responses are elicited in women taking folate supplements, and thus experience a bolus of folate on top of the status achieved by fortification. To characterize this response, we performed gene expression profiling experiments on uterus tissue of pregnant mice after a preconceptional regimen of supplementation with folinic acid. We suggest that folinic acid supplementation affects expression of genes that contribute to protein synthesis and localization, genes that play a role for mitochondrial biology and oxidative phosphorylation, and genes encoding nucleotide-binding proteins, including protein kinases and GTP-binding intracellular signaling factors. The extent of such a response is strongly modulated by the genetic background. Finally, we suggest that folinic acid supplementation in this paradigm may affect histone methylation status, a potential avenue to mechanisms of gene regulation.
No associated publication
Specimen part
View SamplesChronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases are essential regulators of inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. In this study, we found that the ubiquitin ligase Siah2 is a central factor in obesity-related adipose tissue inflammation. When challenged with chronic excess energy intake, Siah2-null mice become obese with enlarged adipocytes, but do not develop obesity-induced insulin resistance. Proinflammatory gene expression is substantially reduced in the Siah2-null epididymal adipose tissue of the obese Siah2KO mice.
The ubiquitin ligase Siah2 regulates obesity-induced adipose tissue inflammation.
Sex, Age, Specimen part
View SamplesAIMS/HYPOTHESIS: Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, such as metabolic syndrome and hypertension. We hypothesized that adverse outcomes from diabetic pregnancies may be linked to compromised placental function. Our goal in this study was to identify cellular and molecular abnormalities in diabetic placenta.
Altered gene expression and spongiotrophoblast differentiation in placenta from a mouse model of diabetes in pregnancy.
Sex, Specimen part
View SamplesHomeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxd4 during cartilage development, we observed severe defects, namely physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, we performed gene expression profiling using the Affymetrix microarray platform.
Microarray Analysis of Defective Cartilage in Hoxc8- and Hoxd4-Transgenic Mice.
Specimen part
View SamplesHomeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxc8 during cartilage development, we observed severe defects, namely physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, we performed gene expression profiling using the Affymetrix microarray platform.
Microarray Analysis of Defective Cartilage in Hoxc8- and Hoxd4-Transgenic Mice.
Specimen part
View SamplesDiabetic embryopathy can affect any developing organ system, although cardiovascular malformations, neural tube defects and caudal dysgenesis syndrome are the most prominent congenital malformations. We hypothesize that the metabolic imbalance occurring in diabetic pregnancy de-regulates tissue specific gene expression programs in the developing embryo. In order to identify genes whose expression is affected by maternal diabetes, we analyzed gene expression profiles of diabetes-exposed mouse embryos by using Affymetrix microarrays. We identified 129 genes with altered expression levels; 21 genes had increased and 108 genes had decreased expression levels in diabetes-exposed embryos relative to controls. A substantial fraction of these genes (35) are essential for normal embryonic development as shown by functional studies in mouse models. The largest fraction of diabetes-affected genes was in transcription factor and DNA-binding/chromatin remodeling functional categories (19%), which directly affect transcription. These findings suggest that transcriptional regulation in the developing embryos is perturbed by maternal diabetes and that transcriptional regulation plays a major role in the responses of embryos to intrauterine exposure to diabetic conditions. Interestingly, we found the expression of hypoxia-inducible factor 1 (Hif1) deregulated in the embryos exposed to the conditions of maternal diabetes. Since hypoxic stress is associated with the complications of diabetic pregnancy, we performed a post-hoc analysis of our microarray data with a specific focus on known HIF1 target genes. Of 39 genes detected in our microarrays, the expression changes of 22 genes (20 were increased and two genes were decreased in diabetes-exposed embryos) were statistically significant. These results indicate that HIF1-regulated pathways are affected in diabetes-exposed embryos. These results strongly suggest that de-regulation of hypoxia/HIF1 activated pathways could be the one of the key molecular events associated with the exposure to the teratogenic intrauterine environment of a diabetic mother.
Maternal diabetes alters transcriptional programs in the developing embryo.
Specimen part
View SamplesExposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs.
Maternal diabetes alters transcriptional programs in the developing embryo.
Specimen part, Disease, Disease stage
View SamplesTo characterize the process of chondrocyte differentiation and maturation, we used Affymetrix GeneChip analysis to profile the dynamic changes in mRNA expression in high density cultures of primary rib chondrocytes from newborn mice. Temporal expression profiles were obtained from RNA harvested from chondrocytes cultured for 2, 6, 9, 12 and 15 days.
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