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

在本报告中，我们的目标是从胚胎干细胞(ES)或诱导多能干细胞(IPS)建立更有效和更实用的内皮细胞分化系统。为此，我们利用芯片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H3K4me3在分化的早期阶段发生了变化。此外，我们还发现了一些双价基因(H3K4me3和H3K27me3双阳性)，如ETV2、Gata2、Sox18、Sox7和Fl1，这些基因在早期上调，被认为是内皮细胞分化的主要调控基因。这些因素的敲除导致内皮细胞分化效率的急剧下降。综上所述，这些发现表明，决定细胞命运的不仅是主要的转录因子，还包括表观遗传的组蛋白修饰。

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.