| 刘涛 刘文超 刘新秀 邓敏 陈静.基于诱导性多潜能干细胞的亨廷顿舞蹈病发病机制研究[J].现代生物医学进展英文版,2016,16(33):6418-6423. |
| 基于诱导性多潜能干细胞的亨廷顿舞蹈病发病机制研究 |
| Pathogenesis Research of Huntington Diseases on Induced Pluripotent StemCells Line |
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| DOI： |
| 中文关键词: 亨廷顿舞蹈病（HD） iPSC 运动神经元 线粒体功能障碍 |
| 英文关键词: Huntington disease iPSC Motor neurons Mitochondrial dysfunction |
| 基金项目:国家自然科学基金项目（81473042）；国家自然科学基金项目（31171048）；河北省自然科学基金项目（H2013209040） |
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| 中文摘要: |
| 目的：基于诱导性多潜能干细胞（induced pluripotent stem cells, iPSC）多潜能性的特点将亨廷顿舞蹈病（Huntington disease,
HD）患者和正常人特异性iPSC 定向诱导分化成运动神经元，并在运动神经元的基础上探讨HD的发病机制。方法：将HD 患者和
正常人的iPS 细胞在特定的生长因子和神经因子的作用下定向诱导分化成运动神经元。然后用免疫荧光染色检测运动神经元特
异性标记物HB9 和ISL1 的表达。以DCFH-DA和JC-1 为荧光探针，利用流式分析法分别对正常人和HD 患者运动神经元细胞
活性氧和线粒体膜电位进行检测。结果：经过25 天诱导分化成功得到HD 患者和正常人的运动神经元，并且免疫荧光染色显示，
茁III-微管蛋白阳性的神经细胞同时表达运动神经元特异性的标志物HB9 和ISL1。此外，经实验统计发现HD 患者运动神经元细
胞内代表活性氧水平的荧光强度（4704.33± 390.50）较正常组（2840.33± 166.20）有明显增强（P=0.002），而且代表线粒体膜电位红
绿荧光强度比（2.74± 0.13）较正常组（3.97± 0.29）相比有明显降低（P=0.03）。结论：HD 患者特异性iPSC能够诱导分化成运动神
经元，为实验提供研究模型。HD 的发病与运动神经元细胞线粒体功能障碍有关。 |
| 英文摘要: |
| Objective:The cells fromHuntington disease (HD) patient and healthy people were induced to differentiate into motor
neurons based on pluripotency characteristic of iPSC, and the motor neurons was used to explore the pathogenesis of HD.Methods:The
iPS cells collected from HD patient and healthy people were differentiated into motor neurons under the action of certain growth factors
and neurotrophic factors. The expression levels of motor neuron specific markers HB9 and ISL1 were evaluated by immunofluorescence
staining. Reactive oxygen species and mitochondrial membrane potential of control and HD patient motor neurons were evaluated by
flow cytometry, and DCFH-DA and JC-1 were used as the fluorescent probes respectively.Results:Successfully differentiated HD patient
and control specific iPS cells into motor neurons after 25 days. And immunofluorescence staining showed that 茁III-tubulin positive neurons
express both motor neuron specific markers HB9 and ISL1. Furthermore, the ROS levels fluorescence intensity of HD patient motor
neurons (4704.33± 390.50) had significantly enhanced. than controls（2840.33± 166.20）(P=0.002), on behalf of the mitochondrial membrane
potential of fluorescence intensity red-green ratio (2.74± 0.13) had significantly reduced than controls (3.97± 0.29) (P=0.03).Conclusion:HD patient-specific iPSC can be differentiated into motor neurons, and provided a model for experimental research. The pathogenesis
of Huntington's disease was associated with mitochondrial dysfunction of motor neurons. |
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