SHANK2基因表达下调对诱导多能干细胞来源神经发育模型早期发育的影响

发布时间：2018-04-01 06:03

  本文选题：SHANK　切入点：诱导性多能干细胞　出处：《暨南大学学报(自然科学与医学版)》2017年03期

【摘要】：目的:探索SHANK2基因表达下调对诱导性多能干细胞神经发育模型的早期影响.方法:体外建立人诱导多能干细胞来源的神经发育模型,构建携带靶向敲减SHANK2基因表达信息shRNA的慢病毒,在发育起点感染细胞模型.在发育第3、6、9、12、15天分别固定细胞,荧光显微镜拍照,动态监测继发于SHANK2表达下调的胞体面积、突起长度与分支、生长锥面积等神经元形态发育变化.结果:体外成功建立人诱导多能干细胞来源的神经发育模型.与sh Control组相比,在发育不同时间点shSHANK2组神经元分支个数减少、突起长度减小,shSHANK2组神经元胞体面积、生长锥面积均有所减小.结论:SHANK2基因敲减导致早期神经元形态发育异常,可能是SHANK2导致自闭症谱系障碍的潜在致病机制之一.
[Abstract]:Objective: to explore the early effect of down-regulation of SHANK2 gene expression on the neural development of induced pluripotent stem cells. Methods: a human induced neural development model of pluripotent stem cells was established in vitro. To construct a lentivirus carrying shRNA, the expression information of targeted knockdown SHANK2 gene, and to infect the cell model at the beginning of development. The cells were fixed separately on the 15th day of development, and the cells were photographed by fluorescence microscope to dynamically monitor the area of the cell body secondary to the down-regulation of SHANK2 expression. Results: the neuronal development model derived from human pluripotent stem cells was successfully established in vitro. At different time points of development, the number of neuronal branches decreased, the length of process decreased, and the cell body area and growth cone area of shSHANK2 group decreased. Conclusion the knockout of the gene of shSHANK2 group leads to the early morphologic abnormality of neurons. It may be one of the underlying pathogenesis of autism spectrum disorder caused by SHANK2.
【作者单位】： 暨南大学粤港澳中枢神经再生研究院;
【基金】：国家自然科学基金项目(31400922)
【分类号】：R749
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本文编号：1694266