Generation of Induced Pluripotent Stem Cells from Skin Fibroblasts of a Patient with Olivopontocerebellar Atrophy
Generation of Induced Pluripotent Stem Cells from Skin Fibroblasts of a Patient with Olivopontocerebellar Atrophy
复制标题
从橄榄桥小脑萎缩患者的皮肤成纤维细胞中产生诱导多能干细胞
DOI：
10.1620/tjem.226.151
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发表时间：
2012-02-01
影响因子：
2.2
通讯作者：
Sun, Xiaofang
中科院分区：
文献类型：
--
作者：
Luo, Yumei;Fan, Yong;Sun, Xiaofang
从患者的体细胞产生诱导多能干（iPS）细胞代表了疾病建模的有力工具，并且它们在细胞治疗中可能具有广泛的应用。橄榄桥脑小脑萎缩症是一种罕见的神经系统疾病，以小脑脑桥和下橄榄核萎缩为特征，伴有运动障碍和协调障碍。在这里，我们报告的一代iPS细胞的皮肤成纤维细胞的56岁的女性患者与家族性OPCA。OPCA被归类为常染色体显性共济失调，也称为脊髓小脑共济失调（SCA）7。患者SCA 7基因的疾病等位基因含有45个CAG三核苷酸重复，其数量大于正常重复数（4至36个CAG重复）。OPCA-iPS细胞通过四种转录因子的异位表达产生：OCT 4、SOX 2、KLF 4和c-MYC。OPCA-iPS细胞表达多能性标志物，并且它们可以在体外和体内分化成各种体细胞类型。此外，iPS细胞还可以定向分化为神经细胞。因此，OPCA-iPS细胞为研究OPCA的疾病机制、发现新药和开发新疗法提供了前所未有的细胞模型。
Generation of induced pluripotent stem (iPS) cells from somatic cells of patients represents a powerful tool for disease modeling, and they may have a wide range of applications in cell therapies. Olivopontocerebellar atrophy (OPCA) is a rare and debilitating neurologic disease of insidious onset, characterized by atrophy of the cerebellum pons and inferior olivary nuclei with concomitant ambulation deficits and dyscoordination. Here, we report the generation of iPS cells from skin fibroblasts of a 56-year-old female patient with familial OPCA. OPCA is classified in the autosomal dominant ataxia that is also named spinocerebellar ataxia (SCA) 7. The disease allele of SCA7 gene of the patient contains 45 CAG trinucleotide repeats, the number of which is larger than the normal repeat number (4 to 36 CAG repeats). The OPCA-iPS cells were generated via ectopic expression of four transcription factors: OCT4, SOX2, KLF4 and c-MYC. The OPCA-iPS cells expressed the pluripotency markers, and they can be differentiated into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells. Therefore, the OPCA-iPS cells offer an unprecedented cell model to investigate disease mechanisms, discover novel drugs, and develop new therapies for OPCA.