血管再生在心血管病和肿瘤中有重要的生理和病理意义。然而其机制十分复杂，目前仍不十分清楚。人胚胎干细胞(hESC)向血管内皮细胞(EC)定向分化可作为研究血管再生的重要模型。我们前期研究发现在hESC中过表达FLI1同时激活蛋白激酶C可以在3天内将90%以上的hESC定向诱导为EC。进一步研究发现CHD家族中的CHD3在这一过程中呈现高表达。敲减CHD3可以明显降低hESC向EC的分化效率。说明CHD3在EC分化中起重要作用,但其机制不明。本研究拟通过敲减/敲除CHD3明确在两种诱导体系中对hESC-EC定向分化表型的具体影响，进而通过将转录组、CHIP-seq、免疫共沉淀质谱等数据综合分析探索其下游信号通路及相互作用蛋白，最后通过基因敲除小鼠模型验证CHD3对小鼠血管再生的影响。该项目的实施有望为血管再生的机制提供新研究思路。

Angiogenesis plays very important roles physiologically and pathologically in both cardiovascular diseases and tumorigenesis. However, the detailed molecular mechanism is still unclear because of its complexity. Directional differentiation from human embryonic stem cells (hESCs) to endothelial cells (ECs) could be a useful cell model for investigation of angiogenesis. Our previous study revealed that overexpression of FLI1, as well as activation of protein kinase C (PKC) simultaneously, could rapidly and evenly differentiate more than 90% hESCs to endothelial progenitor-like cells (iECs) in only 3 days. Further investigation showed that CHD3, a member of CHD superfamily, is significantly upregulated during the induction. Knockdown of CHD3 dramatically decreases the differentiation efficiency, which implies that CHD3 plays an important role in EC differentiation, while the mechanism is far from clear. In this project, we will firstly elucidate the effect of CHD3 to hESC-EC differentiation in two induction systems (including our newly established system) by knockdown/knockout approach. Moreover, the downstream signaling pathway and interacting proteins will be identified by combining the multi-omics data including RNAseq, CHIP-Seq, and mass spectrum followed CHIP. Finally, we will establish knockout mice model to verify the function of CHD3 in angiogenesis. Hopefully, our project will offer a new angle for the mechanism of angiogenesis.