Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sex chromosomes affect gene expression of autoantigen specific CD4+ T cells in B6 gonadal males.

ABSTRACT: To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of autoantigen specific CD4+ T cells from XX and XY- mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE137793 | GEO | 2019/12/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Sex chromsomes affect gene expression of immunized CD4+ T cells in SJL

Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of CD4+ T cells stimuated with anti-CD3/CD28 from XX and XY- mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.

2019-12-10 | GSE139035 | GEO

Sex chromosomes affect gene expression of healthy CD4+ T cells in SJL.

2019-12-10 | GSE137792 | GEO

Sex chromosomes affect gene expression of healthy CD4+ T cells in B6 gonadal females.

Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of CD4+ T cells stimuated with antiCD3/CD28 from XX and XY- mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.

2019-12-10 | GSE137791 | GEO

Sex chromsomes affect gene expression of healthy CD4+ T cells in B6 gonadal males

Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of CD4+ T cells stimuated with antiCD3/CD28 from XXSry and XY-Sry mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.

2019-12-10 | GSE139034 | GEO

Sex chromsomes affect gene expression of autoantigen specific CD4+ T cells.

2019-08-21 | GSE121705 | GEO

Sex chromsomes affect gene expression of autoantigen specific CD4+ T cells

2019-08-21 | GSE121292 | GEO

ERRBS-Seq of XpY*x and XmY*x murine CD4+ T cells

Project description:Most autoimmune diseases have a higher incidence in women than men due to differences in sex hormones, sex chromosomes, or both. Female (XX) and male (XY) sex chromosome complements differ in parent-of-origin of the X chromosome, with females inheriting one each from the mother and father, while males inherit only one from the mother2. Here, we discovered that the paternal X (Xp) had higher DNA methylation than the maternal X (Xm) in autoantigen specific CD4+ T lymphocytes, potentially suppressing X gene expression in XX. Using the “Four Core Genotypes” model, the transcriptomes of autoantigen specific CD4+ T lymphocytes showed higher expression of many X genes in XY- than XX. Expression of toll-like receptor 7 (Tlr7) and forkhead box P3 (FoxP3), two X chromosome genes important in autoimmunity, was higher in XY- than XX, confirming genome wide methylation and transcription data. Thus, parent-of-origin differences in DNA methylation of X genes can lead to sexual dimorphisms in gene expression during autoimmunity.

2019-12-11 | GSE122787 | GEO

Sex chromosome complement defines diffuse versus focal angiotensin II-induced aortic pathology

Project description:Objective-Aortic pathologies exhibit sexual dimorphism, with aneurysms in the ascending, thoracic and abdominal aorta (AAA) exhibiting higher prevalence in males. Despite lower incidence of aortic vascular disease in women, aneurysms progress rapidly. Mechanisms for these sex differences are unclear. We defined the role of sex chromosome complement and testosterone in regional development and progression of angiotensin II (AngII)-induced vascular pathologies. Approach and Results-We used transgenic male mice expressing Sry on an autosome to create low density lipoprotein receptor (Ldlr) deficient male mice with an XY or XX sex chromosome complement. Subjects were then sham operated or orcheictomized. Transcriptional profiling on abdominal aortas from XY or XX males demonstrated1746 genes influenced by sex chromosomes, sex hormones, or an interaction. A second cohort of animals was then infused with AngII for 28 days. Diffuse aortic aneurysm pathology developed in XY AngII-infused males, while XX males developed discrete AAAs. Castration reduced all AngII-induced aortic pathologies in XY and XX males. Thoracic aortas from AngII-infused XY males, but not XX males exhibited adventitial thickening. We infused male XY and XX mice with saline or AngII and quantified mRNA abundance of key genes in thoracic versus abdominal aortas. Regional differences in mRNA abundance existed before AngII infusions, which were differentially influenced by AngII between genotypes. Prolonged AngII infusions resulted in AAA aortic wall thickening in XY males with diffuse aortic pathology, while XX males had dilated focal AAAs. Conclusions-An XY sex chromosome complement mediates diffuse aortic pathology, while an XX sex chromosome complement contributes to discrete AngII-induced AAAs.

2018-07-22 | GSE102143 | GEO

The X chromosome gene Kdm6a modulates multiple immune response genes in CD4+ T cells and is disease promoting in autoimmune disease

Project description:Multiple sclerosis (MS) is a T-cell mediated autoimmune disease that has a sexually dimorphic pattern in disease susceptibility. Consistent with many autoimmune diseases, females are more susceptible than males to MS. Sexual dimorphisms may be due to differences in sex hormones, sex chromosome genes, or both. Regarding sex chromosome genes, a small percentage of X chromosome genes escape the dosage compensation mechanism of X inactivation and have higher expression in females (XX) compared to males (XY). According to the high throughput analysis, the top sexually dimorphic gene with higher expression in CD4+ T cells from females (vs. males) and from XX mice (vs. XY) was Kdm6a, a histone demethylase and transcription factor on the X chromosome. Deletion of Kdm6a specifically in CD4+ T cells ameliorated clinical disease and reduced neuropathology in the classic CD4+ T cell mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). Global transcriptome analysis in CD4+ T cells from EAE mice with a specific deletion of Kdm6a showed upregulation of Th2 and Th1 activation pathways and downregulation of neuroinflammation signaling pathways. Together, this demonstrates that the X escapee Kdm6a regulates multiple immune response genes, providing a mechanism for sex differences in autoimmune disease susceptibility.

2019-10-18 | GSE121703 | GEO

The X chromosome gene Kdm6a modulates multiple immune response genes in CD4+ T cells and is disease-promoting in autoimmune disease

2019-10-18 | GSE128615 | GEO