DNA methylation regulates lineage-specifying genes in the human vascular system [expression array].

During embryonic development, the lymphatic system emerges by transdifferentiation from the cardinal vein. Although lymphatic and blood vasculature share a close molecular and developmental relationship, they display distinct features and functions. However, even after terminal differentiation, transitions between the two endothelial cell types have been reported. Since changes in phenotypic plasticity and cellular differentiation processes frequently involve epigenetic mechanisms, we wondered whether DNA methylation might play a role in regulating cell type-specific expression in endothelial cells. By analyzing global gene expression and methylation patterns of primary human dermal lymphatic and blood endothelial cells, we identified a highly significant set of genes, which were differentially methylated and expressed. Pathway analyses of the differentially methylated and upregulated genes in lymphatic endothelial cells revealed involvement in developmental and transdifferentiation processes. We further identified a set of novel genes, which might be implicated in regulating BEC-LEC plasticity and could serve as therapeutic targets and/or biomarkers in vascular diseases associated with alterations in the endothelial phenotype. Expression profile of 10 lymphatic endothelial cells was compared to that of 6 blood endothelial cells, no replicates, no control samples.