Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.

The circulatory system is one of thefirst to function during development. The earliest event in thesystem's development is vasculogenesis, whereby vascularprogeniter cells form clusters called blood islands, which laterfuse to form capillary networks. There exists a very goodin vitro system that mimics this process. When HUVECs(Human Umbilical Vein Endothelial Cells) are cultured on Matrigel,they spontaneously form a capillary network structure. Twotheoretical models have been proposed to explain the patternformation of this in vitro system. Both models utilizechemotaxis to generate spatial instability, and one modelspecifies VEGF as the chemoattractant. However, there are severalunknown factors concerning the experimental model. First, thepattern formation process occurs at the interface between theliquid medium and Matrigel, and it is unclear whether diffusion inthe liquid or gel is critical. Second, the diffusion coefficientof VEGF, which determines the spatial scale of the capillarystructure, has not been properly measured. In the present study,we modified the experimental system to clarify the effect ofdiffusion in Matrigel, and experimentally measured the diffusioncoefficient of VEGF in this system. The relationship with thespatial scale of the pattern generated is discussed.