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OBJECTIVE: To generate familial ALS patient specific induced pluripotent stem (iPS) cell lines and motor neurons and provide a cell-based disease model for amyotrophic lateral sclerosis (ALS) in Han Chinese. METHODS: iPS cells were derived from familial ALS patient by introducing 4 transcription factors OCT3/4, SOX2, KLF4 and c-MYC into fibroblast cells by retroviruses. Karyotypic analysis, immunofluorescence staining and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to identify the pluripotency of these iPS cell lines. In addition, motor neurons were derived from these iPS cells by inhibiting SMAD pathway. RESULTS: IPS cell lines were established from ALS patient carrying SOD1-V14M mutation.
They had pluripotency and were similar to human ES cells. Furthermore, motor neurons were successfully induced from these iPS cells. CONCLUSION: SOD1-V14M mutation does not affect the reprogramming of fibroblast cells and pluripotency of iPS cells, nor does it prevent differentiation of motor neurons. Furthermore, the above cell-based disease model can recapitulate key aspects of ALS pathogenesis so that it provides an indispensible resource for further elucidating ALS disease pathogenesis and screening appropriate drug candidates in Han Chinese.