光遗传学调控TrkA-MAPK/PI3K信号促进iPSC肠神经分化OA

Objective: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 Sox 10 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.