SMA疾病来源的人iPSC细胞株的建立及FGF信号在人iPSC早期神经分化的作用
发布时间：2018-11-19 10:32
【摘要】：寻找具有多项分化潜能和自我更新能力的细胞是近年来再生医学领域研究的重点课题,而人胚胎干细胞(human embryonic stem cell, hESC)是干细胞应用最佳的备选材料。由于受到伦理学问题和免疫性排斥等方面因素的影响,hESC在临床上的应用面临巨大的障碍。寻找新的干细胞备选材料是目前国内外干细胞研究领域相关专家共同关心的课题之一。人诱导多能分化干细胞(induced pluripotent stem cells, iPSC)技术的发现是近年来干细胞研究领域中一个里程碑式的突破。iPSC技术通过应用逆转录病毒转染系统,在成体细胞中导入一个或几个转录因子,从而使成体细胞重编程为具有多项分化潜能的iPSC。基于不同遗传背景的人多能干细胞系的建立及其多向分化潜能研究可为iPSC的临床应用奠定理论基础。 脊髓性肌萎缩症(spinal muscular atrophy, SMA)包括一组常染色体隐性遗传性神经系统疾病,其中儿童型(Ⅰ-Ⅲ)是由其致病基因—运动神经元生存基因(survival of motor neuron, SMN)—端粒侧拷贝SMN1缺失引起,表现为脊髓前角细胞变性所致的肌无力和肌萎缩,并且本病至今无有效治疗。iPSC技术的问世及其高效的分化为神经元亚型的能力为研究SMA等神经遗传性疾病提供了一种新的有利的工具。 成纤维细胞生长因子(fibroblast growth factor, FGF)家族对于促进细胞分裂增殖和血管生成起着非常重要的作用,近来有相关研究表明FGF能够促进人神经的再生与修复,而且最近有研究发现FGF信号在hESC神经分化中起到积极的促进作用。但是有关FGF信号通路在iPSC早期神经分化中的作用至今仍未见报道。 我们采用逆转录病毒转染系统和慢病毒转染系统成功地建立了正常人来源(TZ1、YZ1)及SMA病人来源的iPSC细胞株(SMA-W1),经相关检测发现它们均具有跟hESC相似的多向分化潜能,同时我们还探讨了FGF信号通路在iPSC早期神经分化中的重要作用,并且发现小分子化合物(purmorphamine)能显著提高iPSC向后脑及脊髓运动神经元分化的效率。我们的研究工作有助于更加深入地了解iPSC神经分化的诱导和调控,并且为iPSC在SMA治疗中的应用提供了理想的细胞模型和坚实的实验基础。
[Abstract]:In recent years, searching for cells with multiple differentiation potential and self-renewal ability has been a key topic in the field of regenerative medicine. Human embryonic stem cell (human embryonic stem cell, hESC) is the best candidate material for the application of stem cells. Due to the influence of ethical problems and immunological rejection, the clinical application of hESC is faced with great obstacles. To search for new stem cell materials is one of the topics concerned by relevant experts in stem cell research at home and abroad. The discovery of human induced pluripotent stem cell (induced pluripotent stem cells, iPSC) technology is a landmark breakthrough in stem cell research in recent years. IPSC technology has been used in retrovirus transfection systems. Introduction of one or more transcription factors into adult cells so that adult cells are reprogrammed as iPSC. with multiple differentiation potentials The establishment of human pluripotent stem cell lines based on different genetic backgrounds and their multidirectional differentiation potential can lay a theoretical foundation for the clinical application of iPSC. Spinal muscular atrophy (spinal muscular atrophy, SMA) includes a group of autosomal recessive nervous system diseases, in which the childhood type (鈪，
本文编号：2342035
[Abstract]:In recent years, searching for cells with multiple differentiation potential and self-renewal ability has been a key topic in the field of regenerative medicine. Human embryonic stem cell (human embryonic stem cell, hESC) is the best candidate material for the application of stem cells. Due to the influence of ethical problems and immunological rejection, the clinical application of hESC is faced with great obstacles. To search for new stem cell materials is one of the topics concerned by relevant experts in stem cell research at home and abroad. The discovery of human induced pluripotent stem cell (induced pluripotent stem cells, iPSC) technology is a landmark breakthrough in stem cell research in recent years. IPSC technology has been used in retrovirus transfection systems. Introduction of one or more transcription factors into adult cells so that adult cells are reprogrammed as iPSC. with multiple differentiation potentials The establishment of human pluripotent stem cell lines based on different genetic backgrounds and their multidirectional differentiation potential can lay a theoretical foundation for the clinical application of iPSC. Spinal muscular atrophy (spinal muscular atrophy, SMA) includes a group of autosomal recessive nervous system diseases, in which the childhood type (鈪，
本文编号：2342035
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