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

本研究的目的是建立一种更有效、实用的胚胎干细胞（ES）或诱导多能干细胞（iPS）向内皮细胞分化的系统。为此，我们采用ChIP-seqs和微阵列两种综合分析方法对小鼠ES细胞的内皮细胞分化系统进行了分析，发现H3 K4 me 3在分化早期发生了变化。此外，我们发现了一些双价基因（H3 K4 me 3和H3 K27 me 3双阳性），如Etv 2，Gata 2，Sox 18，Sox 7和Fli 1，它们在早期时间点上调，应该是内皮细胞分化的主调节因子的候选者。这些因子的敲除导致内皮细胞分化效率的急剧下降。总之，这些发现表明，细胞命运的决定不仅是基于主转录因子，而且还基于表观遗传组蛋白修饰。

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.