人多能干细胞（HPSC)替代疗法治疗帕金森病(PD)已进入临床前期研究。HPSC源中脑多巴胺能（DA）祖细胞移植后分化为A9DA神经元才能促进患者运动功能恢复。然而目前它在宿主脑内异质性地分化为A9、A10DA神经元两种亚群，给患者带来医疗风险。在体研究证实，SOX6是中脑A9DA神经元发育的决定因素。但体外干预SOX6表达对HPSC源DA祖细胞终末分化为A9DA神经元的影响仍不清楚。因此提出假说：体外干预SOX6表达可调控HPSC源DA祖细胞分化为A9DA神经元，可能与调控WNT1/β-catenin信号通路相关。本研究拟选用四种多能干细胞系，采用外源性激动剂和抑制剂调控SOX6表达、病毒转染调控SOX6基因表达等干预手段，通过体外实验和脑内移植实验检测SOX6表达变化对A9DA神经元分化的影响，初步阐明SOX6调控作用及相关机制，为选择性产生A9DA神经元提供新思路和新靶点。

As a promising treatment for Parkinson's disease, Stem cell replacement therapy is near the clinical stage. The midbrain dopamine (DA) progenitor cells derived from human pluripotent stem cells (HPSC) were ony differentiated into A9 DA neurons to recover the movement function of patients with PD. However, it was identified that the midbrain DA progenitor cells were transplanted into the host brain to be differentiated into the two subgroups of dopamine neurons A9 and A10, heterogeneously. The transplant patients would be at risk of medical adverse effects induced by the heterogeneity of differentiation. The experiments were shown that sox6 was a determinant of A9 DA neuron development in vivo. The effect of SOX6 on the terminal differentiation of the midbrain DA progenitor cells into A9 DA neurons remains unclear in vitro. Here, we put forward the following hypothesis: the regulation of SOX6 expression could control DA progenitor cells from HPSC to be differentiatedinto A9 DA neurons in vitro. The mechanism might be related to the regulation of WNT1/ -catenin signaling pathway. Four kinds of pluripotent stem cell lines were selected in this research. After using exogenous agonists and inhibitors, gene expression regulation interventions, the proportion of A9 DA neurons were detected in intro and intracerebral transplantation, to identify the relationship of SOX6 and dopaminergic differentation of HPSC. The regulation mechanism of HDAC1/SOX6/β-catenin on WNT signaling pathway were detected by some methods such as Chromatin Immunoprecipitation Assay. The results of this study woud provide new ideas and new targets for the selective production of A9 DA neurons, and promote the clinical applicaiton.