Genetic and Epigenetic Landscape of Endothelial Cells Differentiation Reveal the Transcriptional Factors Network.

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In this report, our aim is to establish the more efficient and practical endothelial cell differentiation system from embryonic stem (ES) or induced pluripotent stem (iPS) cells. On this purpose, we analyzed the endothelial cell differentiation system from mouse ES cells by using two comprehensive analyses ChIP-seqs and micorarrays.From these experiments we found out H3K4me3 have changed on early stage during differentiation. Moreover, we discovered some bivalent genes (H3K4me3 and H3K27me3 double positive) such as Etv2, Gata2, Sox18, Sox7 and Fli1 which are upregulated at early time points and supposed to be candidates for master regulators of endothelial cells differentiation. Knockdown of these factors caused drastic reduction of endothelial cell differentiation efficiency.Taken together, these findings have suggested that determination of cell fate is based on not only master transcription factors but also epigenetic histone modifications.