DNA methylation regulates lineage-specifying genes in primary lymphatic and blood endothelial cells |
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Authors: | Simone Br?nneke Bodo Brückner Nils Peters Thomas C G Bosch Franz St?b Horst Wenck Sabine Hagemann Marc Winnefeld |
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Institution: | (1) Research and Development, Beiersdorf AG, Hamburg, Germany;(2) Heidelberg, Germany;(3) Zoological Institute, Christian-Albrechts-University, Kiel, Germany; |
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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. |
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