Project description:Mouse ES-cells with different sex chromosome compliment were differentiated into EpiSC, samples were taken every 4-12 hours for 84 hours in total. The original data for the XX-cells is also available as GSE34243, but normalisation of these differs.
Project description:Abdominal aortic aneurysms (AAAs) are a prevalent and deadly human pathology with strong sexual dimorphism. Research demonstrates that sex hormones influence, but do not fully explain, male versus female AAA pathology. In addition to sex hormones, the X and Y sex chromosomes, and their unique complements of genes, may contribute to sexually dimorphic AAA pathology. Here, for the first time, we defined the effect of female (XX) versus male (XY) chromosome complement on AAA formation and rupture in phenotypically female mice using an established murine model. Abdominal aortas from female mice bearing the XY chromosome selectively expressed Y chromosome genes, while genes known to escape X-inactivation were higher in XX females. The majority of gene differences in XY females fell within inflammatory pathways. When XY females were infused with AngII, AAA incidences doubled and aneurysms ruptured. AAAs from XY females exhibited significant inflammation. Moreover, infusion of AngII to XY females augmented aortic activity of matrix metalloproteinases. Finally, testosterone exposure applied chronically, or as a single bolus at postnatal day 1, markedly worsened AAA outcomes in XY compared to XX females. These results demonstrate that an XY sex chromosome complement profoundly influences aortic gene expression profiles and promotes AAA severity.
Project description:Sex biases in the genome-wide distribution of DNA methylation and gene expression levels are some of the manifestations of sexual dimorphism in mammals. To advance our understanding of the mechanisms that contribute to sex biases in DNA methylation and gene expression, we conducted whole genome bisulfite sequencing (WGBS) as well as RNA-seq on liver samples from mice with different combinations of sex phenotype and sex-chromosome complement. We compared groups of animals with different sex phenotypes, but the same genetic sexes, and vice versa, same sex phenotypes, but different sex-chromosome complements. We also compared sex-biased DNA methylation in mouse and human livers. Our data show that sex phenotype, X-chromosome dosage, and the presence of Y chromosome shape the differences in DNA methylation between males and females. We also demonstrate that sex bias in autosomal methylation is associated with sex bias in gene expression, whereas X-chromosome dosage-dependent methylation differences are not, as expected for a dosage-compensation mechanism. Furthermore, we find partial conservation between the repertoires of mouse and human genes that are associated with sex-biased methylation, an indication that gene function is likely to be an important factor in this phenomenon.
Project description:Comparison among ES, EC, TS, NS, differentiated neural cells derived from NS and placenta in addition to ES-N2B27 neural induction. Keywords: cell type comparison design,development or differentiation design,time series design
Project description:To characterize the differentiation by Sox2 KO, we performed microarray analyses of mouse ES cell line 2TS22C during the time-course being induced of Sox2 KO Keywords: development or differentiation design,time series design
Project description:Description: The pluripotency of an embryonic stem cell makes it an attractive target for differentiation strategies aimed at producing tissues for therapeutic purposes. Yet, even though we know that ES cells have tremendous capacity for differentiation, we do not fully understand the molecular paths taken by these cells as they differentiate. In addition, it is unclear how important the removal of leukemia inhibitory factor is to ES cell differentiation. Moreover, it is unclear how the path of ES cell differentiation relates to the molecular decisions made by tissues undergoing normal development. The motivation behind this work is to increase our understanding of this relationship and its potential limitations. Dataset is a murine embryonic stem cell differentiation timecourse consisting of 14 timepoints spanning 17 days of differentiation. Samples were harvested at 24 hour intervals on days 0,1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 15, and 17. There two replicates of each sample in this series. Additionally, there are 14 identically stated differentiation samples, where growth was conducted in ES cell media containing LIF. A common reference design was employed. Groups of assays that are related as part of a time series. Compound Based Treatment: Treatment or lack of treatment with LIF Elapsed Time: Samples were harvested at 24 hour intervals on days 0,1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 15, and 17 Keywords: time_series_design