Project description:Introduction: The dynamics of colorectal epigenetics during early carcinogenesis remain undocumented. In this study, we explore the DNA methylation dynamics in colorectal cancer oncogenesis from non-tumor colon tissues to low-grade, high-grade adenoma and adenocarcinoma. Methods: The methylome of 13 low-grade and 19 high-grade colorectal adenomas was determined using the EPIC v1 Human Methylation Beadchip. These methylation profiles were complemented with the methylomes of 206 non-tumor colon and 24 colon adenocarcinomas from GSE149282, GSE132804 series and the HCMI study. Differentially methylated CpG were identified by Student's t-test and used to monitor the evolution of the colon methylome during carcinogenesis. The differentially methylated promoters were used to infer the associated biological process using gene ontology. Results: 4.9% of the colon methylome is significantly altered (p < 10-4) during carcinogenesis with two thirds corresponding to DNA demethylation. 56.6% of the methylation changes occurs at the transition from non-tumor colon tissues to low-grades adenomas. 18.2% of the DNA methylation changes are transitory during low-grade and/or high-grade adenomas. The biological pathways sensory perception of odor and stimulus were early unmethylated, nervous system development and homophilic cell adhesion were early methylated, and chemical synaptic transmission and cell adhesion were transiently methylated. Conclusion: This study provides insight into the dynamics of colonic epigenetics during carcinogenesis, with early DNA methylation changes in the low-grade adenomas associated with transient DNA methylation changes. However, the causality of these changes remains to be elucidated.
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.
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: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. Two-condition experiment, KP MSCs vs. 3A6 MSCs.
Project description:SPO11-promoted DNA double-strand breaks (DSBs) formation is a crucial step for meiotic recombination, and it is indispensable to detect the broken DNA ends accurately for dissecting the molecular mechanisms behind. Here, we report a novel technique, named DEtail-seq (DNA End tailing followed by sequencing), that can directly and quantitatively capture the meiotic DSB 3’ overhang hotspots at single-nucleotide resolution.