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

YUMEI LUO,¹ YONG FAN,¹ BORONG ZHOU,² ZHIQIANG XU,² YAOYONG CHEN¹ and XIAOFANG SUN¹

¹Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, P.R. China
²Department of Neurology, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, P.R. China

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.

keywords —— disease model; induced pluripotent stem cells; olivopontocerebellar atrophy; screening drugs; therapy

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Tohoku J. Exp. Med., 2012, 226, 151-159

Correspondence: Xiaofang Sun, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, P.R. China.

e-mail: xiaofangsun@hotmail.com