Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical College, P.R. China.
Tohoku J Exp Med. 2012 Feb;226(2):151-9. doi: 10.1620/tjem.226.151.
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.
从患者体细胞中生成诱导多能干细胞（iPS 细胞）是疾病建模的有力工具，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（OPCA）是一种罕见的、进行性的神经退行性疾病，其特征为小脑脑桥和下橄榄核萎缩，伴有运动功能障碍和协调障碍。在此，我们报告了从一位 56 岁女性家族性 OPCA 患者的皮肤成纤维细胞中生成 iPS 细胞。OPCA 被归类为常染色体显性共济失调症，也称为脊髓小脑共济失调症（SCA）7。该患者 SCA7 基因突变体含有 45 个 CAG 三核苷酸重复序列，其数量大于正常重复数量（4-36 个 CAG 重复序列）。通过异位表达四个转录因子：OCT4、SOX2、KLF4 和 c-MYC，生成了 OPCA-iPS 细胞。OPCA-iPS 细胞表达多能性标志物，并且可以在体外和体内分化为各种体细胞类型。此外，iPS 细胞还可以定向分化为神经细胞。因此，OPCA-iPS 细胞为研究疾病机制、发现新药物和开发 OPCA 的新疗法提供了前所未有的细胞模型。
