We report a multi-omic study of sex differences and gene-by-sex interactions across a panel of 100 inbred strains of mice (the Hybrid Mouse Diversity Panel, HMDP), with a focus on metabolic and cardiovascular traits. For all traits examined, including obesity, insulin resistance, fatty liver, atherosclerosis, and gut microbiota composition, sex differences were influenced by genetic background. Loci identified by genome-wide association studies (GWAS) of the traits were frequently influenced by sex. Lyplal1, a gene implicated in human obesity, was shown to underlie a sex-specific locus for diet induced obesity. Many of the sex-dependent traits showed interdependencies as judged by correlation and shared gene expression patterns, indicating higher order regulation. Global gene expression analyses of tissues across the HMDP indicated that sex differences in mitochondrial functions in adipose contributed to many of the traits. Consistent with this, we observed that females tended to be more resistant to the adverse effects of a high fat diet, with smaller adipocytes and increased “browning” of white adipose tissue as compared to males. Sex-specific differences in mitochondrial activity were confirmed by examining respiration of isolated mitochondria. Gonadectomy experiments revealed thousands of genes influenced by sex hormones. In liver, a tissue exhibiting particularly strong differences in gene expression between tissues, sex hormones appeared to be the primary driver of the differences, whereas in adipose organizational effects of sex appeared to be more important. Overall design: Sixteen male and sixteen female C57BL/6J were purchased from The Jackson Laboratory (Bar Harbor). Mice were either maintained on a chow diet (Ralston Purina Company) or placed on an HF/HS diet (Research Diets D12266B) at 8 weeks of age until 16 weeks of age. At 6 weeks of age the mice were gonadectomized under isoflurane anesthesia. Scrotal regions of male mice were bilaterally incised, testes removed, and the incisions closed with wound clips. Ovaries of female mice were removed through an incision just below the rib cage. There were four mice per group. The muscle layer was sutured, and the incision closed with wound clips. In sham-operated control mice, incisions were made and closed as described above. The gonads were briefly manipulated, but remained intact. Gonadal fat and liver samples were taken for RNASeq expression profiling.
Gene-by-Sex Interactions in Mitochondrial Functions and Cardio-Metabolic Traits.
Sex, Age, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic architecture of insulin resistance in the mouse.
Sex, Age, Specimen part
View SamplesIdentify genes in the gonadal adipose tissue whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Genetic architecture of insulin resistance in the mouse.
Sex, Age, Specimen part
View SamplesIdentify genes in the liver whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Genetic architecture of insulin resistance in the mouse.
Sex, Age, Specimen part
View SamplesIdentify genes in the epididymal adipose tissue whose expression is under genetic regulation in the hybrid mouse diversity panel. The hybrid mouse diversity panel is comprised of classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Bennett et al Genome Research 2010. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice.
Sex, Age, Specimen part
View SamplesBackground. Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is not well characterized. Markers of these processes may provide a deeper understanding of the underlying mechanisms. Objective. To identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss. Design. RNA from subcutaneous abdominal adipose tissue from nine obese subjects was obtained and analyzed at baseline, after weight reduction on a low calorie diet (LCD), and after a period of group therapy in order to maintain weight stability. Results. Subjects lost 18.8 + 5.4% of their body weight during the LCD and maintained this weight during group therapy. Insulin sensitivity (HOMA) improved after weight loss with no further improvement during weight maintenance. Cyclin-dependent kinase inhibitor 2B (CDKN2B) and JAZF zinc finger 1 (JAZF1), associated with type 2 diabetes, were downregulated. We could also confirm the downregulation of candidates for obesity and related traits, such as tenomodulin (TNMD) and matrix metallopeptidase 9 (MMP9), with weight loss. The expression of other candidates, such as cell death-inducing DFFA-like effector A (CIDEA) and stearoyl-CoA desaturase (SCD) were upregulated during weight loss but returned to baseline levels during weight maintenance. Conclusion. Genes in the adipose tissue are differentially expressed during weight loss and weight maintenance after weight loss. Genes that show sustained regulation may be of potential interest as markers of the beneficial effects of weight loss whereas others seem to be primarily involved in the process of weight loss itself.
Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance.
Sex, Age
View SamplesThe pathogenic mechanisms of common kidney glomerular diseases, including the vast majority of cases of proteinuria, remain unknown.
Glomerular transcriptome changes associated with lipopolysaccharide-induced proteinuria.
No sample metadata fields
View SamplesAt least 30 types of retinal ganglion cell (RGC) send distinct messages through the optic nerve to the brain. Strategies for promoting regeneration of RGC axons following injury act on only some of these types. Here we tested the hypothesis that over-expressing developmentally important transcription factors in adult RGCs could reprogram them to a “youthful” growth-competent state and promote regeneration of other types. From a screen of transcription factors expressed by developing RGCs, we found one, Sox11, that induced substantial axon regeneration. Transcriptome profiling confirmed that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, alpha-RGCs, which preferentially regenerate following treatments such as PTEN deletion, were killed by Sox 11. Thus, Sox 11 promotes regeneration of non-alpha RGCs, which are refractory to PTEN. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state and that different growth-promoting interventions act on distinct neuronal types. Overall design: We compared transcriptomes of retinal ganglion cells between AAV-Control retinas, and retinas treated with AAV-Sox11 overexpression. We then performed optic nerve crush, and 3 days later purified RGCs using FACS. RGCs were marked with Thy1-PE-Cy7 antibody and with live/dead cell staining. We performed sample preparations in full triplicate, and in each replicate we always performed Control and Sox11 on the same day, in alternating order.
Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others.
Specimen part, Subject
View SamplesAtopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. The goal of this study was to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD.
Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.
Specimen part, Disease
View SamplesExamine global gene expression patterns in control and 35S:PAP1 Arabidopsis plants upon environmental perturbation (light and temperature) over the course of the experiments.
Environmental regulation of leaf colour in red 35S:PAP1 Arabidopsis thaliana.
No sample metadata fields
View Samples