人源诱导多能干细胞分化神经元的发育动力分析

Developmental motility analysis of human induced pluripotent stem cells-derived neuron

目的:建立人诱导多能干细胞(iPSC)神经发育模型,探究不同发育时期神经元胞体和突起的动力规律.方法:采用正常人iPSC神经发育模型,将iPSC诱导成神经前体细胞(NPC),再分化为神经元,取贴壁分化到第5天的神经元(早期)和贴壁分化到第15天的神经元(中晚期),对两组神经元胞体和突起进行5 h动态追踪.结果:在神经发育过程中,神经元胞体和突起运动速度降低、神经元突起总长度增加和突起总数量减少.与第15天神经元相比,第5天神经元(早期)胞体运动速度显著提高;通过对比两组神经元运动轨迹,第5天神经元(早期)胞体运动范围更广、运动方向更随机;与第15天神经元相比,第5天神经元(早期)一级突起生长速度和坍塌修剪速度显著提高.结论:神经元胞体运动和突起生长坍塌修剪过程均表现出早期活跃于中晚期,提示可在神经元发育早期对神经元动力进行干预和研究,为自闭症等神经发育障碍疾病神经元动力异常的早期干预提供了理论依据.

Objective:The neural development model of human induced pluripotent stem cells(iPSC)was established to explore the motility of neuron soma and neurite in different developmental courses.Methods:iPSC were induced into neural precursor cells,and then derived to neurons,iPSC derived neurons were divided into early course group(the neurons that adhere to the 5th day)and mid-late course group(the neurons that adhere to the 15th day).The neurons were dynamically tracked for 5 hours.Results:During neuronal development,the motility of neuron soma and neurite was more inactive,the total neurite length was increased and the total branches number was decreased.Compared with the mid-late course group(day15),the motility speed of neuron soma in the early course group(day5)was significantly increased;The motility range was wider and the motility direction was more random in the early course group(day5)by comparing the movement trajectories of the two groups;At the meanwhile,the extend and retract motility speed of neuron neurite was significantly increased in the early course group(day5).Conclusion:Neuron soma motility and the extension and retraction of neurite were active in the early course,suggesting that neural motility can be intervened and studied in the early course of neural development,providing a theoretical basis for the early intervention of abnormal neural motility in neurodevelopmental disorders,such as autism.