title: DNA methylation regulates lineage-specifying genes in primary lymphatic and blood endothelial cells.
abstract: 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 blood endothelial cells (BEC) and lymphatic endothelial cells (LEC) have been reported. Since phenotypic plasticity and cellular differentiation processes frequently involve epigenetic mechanisms, we hypothesized that 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 LEC and BEC, we identified a highly significant set of genes, which were differentially methylated and expressed. Pathway analyses of the differentially methylated and upregulated genes in LEC 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.
authors.affiliation: Research and Development, Beiersdorf AG, Hamburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Brönneke
authors.forename: Bodo
authors.initials: B
authors.lastname: Brückner
authors.forename: Nils
authors.initials: N
authors.lastname: Peters
authors.forename: Thomas C G
authors.initials: TC
authors.lastname: Bosch
authors.forename: Franz
authors.initials: F
authors.lastname: Stäb
authors.forename: Horst
authors.initials: H
authors.lastname: Wenck
authors.forename: Sabine
authors.initials: S
authors.lastname: Hagemann
authors.forename: Marc
authors.initials: M
authors.lastname: Winnefeld
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009928:Organ Specificity / Q000502:physiology