从干细胞分化获得有功能的血管平滑肌细胞是血管再生治疗的基础。我们发现转录因子Bach1在人胚胎干细胞中高表达，Bach1基因敲除促进干细胞向血管平滑肌细胞分化和平滑肌细胞的收缩，Bach1与转录因子KLF4有结合，但是Bach1如何调控人胚胎干细胞向血管平滑肌细胞分化尚不清楚。本课题拟在Bach1基因敲除和诱导性Bach1过表达的人胚胎干细胞上，研究Bach1是否与KLF4形成一个转录复合体，结合在Myocardin基因启动子区抑制其表达，进而抑制平滑肌标志分子表达，抑制人胚胎干细胞向血管平滑肌细胞分化；研究Bach1对人胚胎干细胞分化的血管平滑肌细胞Ca2+释放和收缩功能的影响。在免疫缺陷小鼠细胞移植模型上，研究Bach1对血管平滑肌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平滑肌细胞分化的分子机制，为血管再生治疗提供新策略。

Obtaining functional vascular smooth muscle cells (VSMCs) derived from stem cells is the basis for the vascular regeneration therapy. We found that Bach1 is highly expressed in human embryonic stem cells (hESC), and knockout of Bach1 promoted the differentiation of VSMCs from stem cells and enhanced the contractile function of VSMCs. Bach1 bound to the transcript factor KLF4, but the role of Bach1 in the differentiation of VSMCs from human embryonic stem cells is largely uncharacterized. In the present study, by using Bach1 knockout and inducible Bach1 overexpressed hESC, we will determine whether Bach1 forms a transcriptional complex with KLF4, binds to the promoter of myocardin and inhibits the transcription of myocardin, and then suppresses the expression of VSMC makers, thus inhibits the differentiation of hESCs toward VSMCs. The role of Bach1 in the Ca2+ release and contractile function of VSMCs derived from hESC will be studied. By using cell transplantation model in immune deficient mice, we will investigate the role Bach1 in VSMCs for the formation of blood vessels in mice. This study may provide the molecular mechanisms of Bach1 in the regulation of differentiation of VSMCs and give the scientific basis for the vascular regeneration therapy.