Project description:Mesenchymal stem/stromal cells (MSCs) were harvested from subcutaneous adipose tissue of patients with obesity or healthy controls and expanded for 3-4 passages, and 5hmC profiles were examined through hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq). We hypothesized that obesity and cardiovascular risk factors induce functionally-relevant, locus-specific changes in overall exonic coverage of 5hmC in human adipose-derived MSCs.
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)
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.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Animal studies have linked disturbed adipose tissue clock gene rhythms to the pathophysiology of the metabolic syndrome. However, data on molecular clock rhythms in human patients are limited. Therefore, in a standardized real life setting, we compared diurnal gene expression profiles in subcutaneous adipose tissue between obese patients with type 2 diabetes and age-matched healthy lean control subjects, using RNA sequencing. In patients, 1.8% (303 genes) of expressed genes showed significant diurnal rhythms, compared to 8.4% (1421 genes) in healthy controls. In patients, the core clock genes showed reduced amplitude oscillations. Enrichment analysis revealed a loss of rhythm in canonical metabolic pathways including AMPK signaling and cAMP mediated signaling in patients. In conclusion, we provide the first transcriptomics atlas of human adipose tissue diurnal rhythms, and show evidence of decreased diurnal clock and metabolic gene expression rhythms in subcutaneous adipose tissue of obese patients with type 2 diabetes.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.