Wang Lixia, Yi Fei, Fu Lina, Yang Jiping, Wang Si, Wang Zhaoxia, Suzuki Keiichiro, Sun Liang, Xu Xiuling, Yu Yang, Qiao Jie, Belmonte Juan Carlos Izpisua, Yang Ze, Yuan Yun, Qu Jing, Liu Guang-Hui
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Protein Cell. 2017 May;8(5):365-378. doi: 10.1007/s13238-017-0397-3. Epub 2017 Apr 11.
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 and FUS mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.
肌萎缩侧索硬化症（ALS）是一种复杂的神经退行性疾病，其细胞和分子机制尚未完全阐明。包括超氧化物歧化酶1（SOD1）和融合蛋白（FUS）在内的多个基因的突变与家族性ALS相关。在此，我们报告了分别从携带SOD1和FUS突变的家族性ALS患者的成纤维细胞中诱导生成多能干细胞（iPSC）。我们还使用CRISPR/Cas9系统生成了基因校正的ALS-iPSC。对源自SOD1和校正后的iPSC的运动神经元进行全基因组RNA测序（RNA-seq）分析，发现了899个异常转录本。我们的工作可能有助于发现ALS中失调的早期生物标志物和通路，并为治疗ALS的新治疗策略提供依据。
