【作者】 杨凡；

【导师】 张灼华；

【作者基本信息】 中南大学 ， 遗传学， 2012， 硕士

【摘要】 诱导多潜能干细胞(induced Pluripotent Stem cells, iPSCs)是通过特定的化合物处理或特定基因导入终末分化细胞,如人表皮成纤维细胞(Human Dermal Fibroblasts, HDFs),将终末分化的细胞诱导成为多潜能干细胞。诱导多潜能干细胞在形态,增殖,多潜能细胞标记物,基因表达,多潜能基因的表观遗传状态,端粒酶活性等一系列指标上与胚胎干细胞相似。通过体内和体外分化,诱导多潜能干细胞能够分化出三个胚层的细胞。帕金森病(Parkinson’s Disease, PD)是一种最常见的中枢神经系统退行性运动障碍疾病。帕金森病的主要病理症状包括中脑黑底基质多巴胺能神经元的丢失及存活神经元中异常蛋白沉积路易小体(Lewy Body)的形成。由于缺乏有效模拟帕金森病的细胞和动物模型,帕金森病的研究受到了一定的限制。来源于帕金森病病人的诱导多潜能干细胞带有病人的遗传背景,而且能够分化成多巴胺能神经元,可能成为一种非常有效的细胞模型。我们通过收集正常对照,散发型以及家族性帕金森病病人皮肤样本,构建了5个正常,5个散发型,4个家族型帕金森病的iPS细胞系,为进一步研究帕金森病的发病机制提供新的细胞模型。更多还原

【Abstract】 Induced pluripotent stem cell is a type of pluripotent stem cell derived from terminally differentiated cells either by chemical treatment or forced expression of specific genes. Induced pluripotent stem cells are similar to embryonic stem (ES) cells, in many aspects, such as the expression of certain stem cell genes, chromatin methylation patterns, doubling time, embryoid body formation, teratoma formation, and pluripotency and differentiability. Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder. The pathological features of PD include dopaminergic neurons (DA) degeneration in the Substantial Nigra of middle brain and the formation of Lewy Body. Because of the lack of animal and cell models mimicking human PD, molecular mechanisms of PD pathogenesis remain largely unknown. The iPSCs derived from PD patients harbor genetic background of the patients and can be differentiated to dopaminergic neurons. In this study, we have generated iPS Cell lines from HDF of five sporadic PD patients, four familial PD patients and five normal control individuals. These iPS cell lines will likely form novel models to study pathogenic mechanism of PD.更多还原