目的：探索通过细胞移植再生先天性巨结肠症（Hirschsprung Disease，HD）病变肠段的肠神经丛。方 法：采用光遗传学工具，靶向小鼠肠神经前体细胞（Enteric neural progenitor cells，ENPCs）中TrkA相关下游 信号通路，检测其对ENPCs的增殖，迁移和神经分化的影响。结果：采用诱导小鼠多能干细胞（Induced pluripotent stem cell，iPSC），使其表达ENPCs相关标记物Sox10和Nestin。来源于携带有Sox10突变的HD模型 小鼠的ENPCs表现出细胞增殖、迁移以及神经分化能力下调。使用光遗传学工具刺激TrkA，可上调Erk与 Akt磷酸化水平，激活下游MAPK与PI3K信号通路，并增强ENPCs的迁移能力和神经标记物Tuj1的表达水 平。结论：采用光遗传学工具可有效激活TrkA信号通路，并提高ENPCs的细胞迁移、增殖及神经分化能力。

To determine whether enteric ganglia regeneration via cell transplantation can ameliorate postoperative bowel dysfunction following conventional surgery and restore normal intestinal function in Hirschsprung disease (HD). Methods: An optogenetic tool was employed to activate TrkA signaling in mouse enteric neural progenitor cells (ENPCs). Downstream signaling activation and ENPC proliferation, migration, and neuronal differentiation were evaluated in vitro. In addition, the effects of optogenetic TrkA activation on ENPC behavior after transplantation were examined. Results: Mouse induced pluripotent stem cell (iPSC) were differentiated into ENPCs expressing Sox10 and Nestin. ENPCs derived from the HD model exhibited impaired proliferation, migration, and neuronal differentiation. Optogenetic activation of TrkA increased phosphorylation of Erk and Akt, consistent with activation of the MAPK and PI3K pathway. Following transplantation, TrkA activation enhanced ENPC migration and increased expression of the neuronal marker Tuj1. Conclusion: Optogenetic activation of TrkA signaling promotes ENPC migration, proliferation, and neuronal differentiation, supporting a potential strategy for enteric nervous system regeneration in HD.