Homo sapiens
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PROVIDER: PRJNA173243 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion.
2012-06-02 | GSE38396 | GEO
Project description:Despite overwhelming evidence supporting the role of genetics in susceptibility tocomplex diseases, such as autoimmune disorders, a fundamental unresolved questionis whether large numbers of sequence variants with small effect sizes can alter thespatial genome organization. Here, we provide the first report on the reconfiguration ofthe 3D genome due to nucleotide differences associated with type 1 diabetes, anautoimmune disorder. We show that the chromatin organization at T cell identity genesis identical between diabetes-susceptible and diabetes-resistant mouse strains despitethousands of sequence polymorphisms, suggesting that these loci are epigeneticallyresilient to genetic variation. However, molecular and optical mapping of genomefolding demonstrate that diabetes risk-conferring loci coalesce into close spatialproximity in T cells of diabetes-susceptible mice, forming regulatory cliques, andresulting in aberrant gene expression. Our data uncover 3D chromatin architecture asa new dimension in understanding complex diseases
2020-02-11 | GSE141852 | GEO
Project description:Despite overwhelming evidence supporting the role of genetics in susceptibility tocomplex diseases, such as autoimmune disorders, a fundamental unresolved questionis whether large numbers of sequence variants with small effect sizes can alter thespatial genome organization. Here, we provide the first report on the reconfiguration ofthe 3D genome due to nucleotide differences associated with type 1 diabetes, anautoimmune disorder. We show that the chromatin organization at T cell identity genesis identical between diabetes-susceptible and diabetes-resistant mouse strains despitethousands of sequence polymorphisms, suggesting that these loci are epigeneticallyresilient to genetic variation. However, molecular and optical mapping of genomefolding demonstrate that diabetes risk-conferring loci coalesce into close spatialproximity in T cells of diabetes-susceptible mice, forming regulatory cliques, andresulting in aberrant gene expression. Our data uncover 3D chromatin architecture asa new dimension in understanding complex diseases
2020-02-11 | GSE141847 | GEO
Project description:Despite overwhelming evidence supporting the role of genetics in susceptibility tocomplex diseases, such as autoimmune disorders, a fundamental unresolved questionis whether large numbers of sequence variants with small effect sizes can alter thespatial genome organization. Here, we provide the first report on the reconfiguration ofthe 3D genome due to nucleotide differences associated with type 1 diabetes, anautoimmune disorder. We show that the chromatin organization at T cell identity genesis identical between diabetes-susceptible and diabetes-resistant mouse strains despitethousands of sequence polymorphisms, suggesting that these loci are epigeneticallyresilient to genetic variation. However, molecular and optical mapping of genomefolding demonstrate that diabetes risk-conferring loci coalesce into close spatialproximity in T cells of diabetes-susceptible mice, forming regulatory cliques, andresulting in aberrant gene expression. Our data uncover 3D chromatin architecture asa new dimension in understanding complex diseases
2020-02-11 | GSE141846 | GEO
Project description:Despite overwhelming evidence supporting the role of genetics in susceptibility tocomplex diseases, such as autoimmune disorders, a fundamental unresolved questionis whether large numbers of sequence variants with small effect sizes can alter thespatial genome organization. Here, we provide the first report on the reconfiguration ofthe 3D genome due to nucleotide differences associated with type 1 diabetes, anautoimmune disorder. We show that the chromatin organization at T cell identity genesis identical between diabetes-susceptible and diabetes-resistant mouse strains despitethousands of sequence polymorphisms, suggesting that these loci are epigeneticallyresilient to genetic variation. However, molecular and optical mapping of genomefolding demonstrate that diabetes risk-conferring loci coalesce into close spatialproximity in T cells of diabetes-susceptible mice, forming regulatory cliques, andresulting in aberrant gene expression. Our data uncover 3D chromatin architecture asa new dimension in understanding complex diseases
2020-02-11 | GSE141845 | GEO
Project description:The transcriptional output of each cell type is controlled by thousands of enhancers, many of which contain genetic risk variants for common diseases such as type 2 diabetes (T2D). To gain insight into how enhancer variation influences diabetes risk, we created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated islet enhancers with their target genes, often located hundreds of kilobases away. We identified hubs that show spatial and functional connections between enhancersand target genes related to islet function and diabetes. We demonstrate that genetic variants distributed across hub enhancers have a major impact on T2D heritability, and use this knowledge to identify individuals in whom islet regulatory variation has a prominent role in T2D risk. Our results demonstrate the importance of 3D chromatin architecture for molecular interpretation of T2D genetic association signals, and define genomic spaces that harbor a distinct component of the T2D polygenic burden.
| EGAS00001002917 | EGA
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
2012-06-01 | E-GEOD-38396 | biostudies-arrayexpress
Project description:Glucocorticoid signaling in pancreatic islets modulates gene regulatory programs and genetic risk of type 2 diabetes
| PRJNA703993 | ENA
Project description:Ovarian Tumor Risk and Environmental and Genetic Factors
| PRJNA302696 | ENA
Project description:Type 2 diabetes is a complex, systemic disease affected by both genetic and environmental factors. Previous research has identified genetic variants associated with type 2 diabetes risk, however gene regulatory changes underlying progression to disease are still largely unknown. We investigated RNA expression changes that occur during diabetes progression using a two-stage approach. In our discovery stage, we compared changes in gene expression using two longitudinally collected blood samples from subjects who transitioned to type 2 diabetes between the time points against those who did not with a novel analytical network approach. Our network methodology identified 17 networks, one of which was significantly associated with transition status. This 822-gene network harbors many genes novel to the type 2 diabetes literature, but is also significantly enriched for genes previously associated with type 2 diabetes in GWAS. In the validation stage, we queried associations of genetically determined expression with diabetes-related traits in a large biobank with linked electronic health records. We observed a significant enrichment of genes in our identified network whose genetically determined expression is associated with type 2 diabetes and other metabolic traits and validated 31 gene-level associations that have never been reported by previous type 2 diabetes GWAS. Finally, we performed functional validation, demonstrating that the genes in this network are enriched in enhancers that operate in human pancreatic islet cells. We present an innovative and systematic approach that identified and validated key gene expression changes associated with type 2 diabetes transition status and demonstrated their translational relevance in a large clinical resource.
2021-09-16 | GSE184050 | GEO