从干细胞分化获得血管内皮细胞是血管再生治疗的基础。我们发现转录因子Bach1基因敲除抑制人胚胎干细胞向血管内皮细胞分化，Bach1促进血管内皮细胞生长因子受体2（VEGFR2）及内皮细胞分化相关基因的表达，但是Bach1如何调控干细胞向血管内皮细胞分化尚不清楚。本课题拟在人胚胎干细胞向血管内皮细胞分化过程中，研究Bach1是否与精氨酸甲基转移酶PRMT5和赖氨酸甲基转移酶WDR82/SET1A形成复合体，结合在VEGFR2及内皮分化相关基因启动子上，使启动子区H3R2me2s和H3K4me3修饰增加进而促进其表达，促进血管内皮细胞的分化；研究Bach1对干细胞分化而来的血管内皮细胞功能的影响；在免疫缺陷小鼠下肢缺血模型上，研究Bach1对干细胞分化而来的血管内皮细胞在小鼠体内形成血管的影响。这项研究将阐明Bach1调控人胚胎干细胞向血管内皮细胞分化的分子机制，为血管再生治疗提供新策略。

Obtaining functional vascular endothelial cells (VECs) derived from stem cells is the basis for the vascular regeneration therapy. We found that knockout of Bach1 inhibited the differentiation of VECs from human embryonic stem cells (hESCs). Bach1 promotes the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and endothelial cell differentiation-related genes, but the role of Bach1 in the differentiation of VECs from hESCs is not clarified. In the present study, we will determine whether Bach1 forms a transcriptional complex with PRMT5 and WDR82/ SET1A, binds to the promoter of VEGFR2 and endothelial cell differentiation-related genes, increases H3R2me2s and H3K4me3 modification in the promoter region and promotes the expression of VEC makers during the differentiation of hESCs into vascular endothelial cells, thus promotes the differentiation of hESCs toward VECs. The role of Bach1 in the function of VECs derived from hESCs will be studied. In the model of lower limb ischemia in immunodeficient mice, we will investigate the effect of Bach1 on the formation of blood vessels in VECs derived from hESCs. This study will clarify the molecular mechanisms of Bach1 in the regulation of differentiation of VECs and provide the scientific basis for the vascular regeneration therapy.