CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

作     者：Lixia Wang Fei Yi Lina Fu Jiping Yang Si Wang Zhaoxia Wang Keiichiro Suzuki Liang Sun Xiuling Xu Yang Yu Jie Qiao Juan Carlos Izpisua Belmonte Ze Yang Yun Yuan Jing Qu Guang-Hui Liu 

作者机构：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 University of Chinese Academy of Sciences Beijing 100049 China Department of Molecular and Cellular Physiology Stanford University School of Medicine Stanford CA 94305 USA Department of Neurology Peking University First Hospital Beijing 100034 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Universidad Catolica San Antonio de Murcia (UCAM) Campus de los Jeronimos N 135 Guadalupe 30107 Murcia Spain Department of Gynecology and Obstetrics Peking University Third Hospital Beijing 100191 China Beijing Hospital of the Ministry of Health Beijing 100730 China Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Jinan University Guangzhou 510632 China Beijing Institute for Brain Disorders Capital Medical University Beijing 100069 China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2017年第8卷第5期

页      面：365-378页

核心收录：

学科分类：07[理学] 08[工学] 

基　　金：National Basic Research Program of China (973 Program) [2015CB964800, 2014CB964600, 2014CB910503] National High Technology Research and Development Program of China [2015AA020307] CAS [XDA01020312, KJZDEW-TZ-L05, CXJJ-16M271] National Natural Science Foundation of China [1625009, 81330008, 31222039, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, 81401159, 31671429, 81601233, 81671377, 31601109, 31601158] Beijing Natural Science Foundation [7141005, 5142016] Program of Beijing Municipal Science and Technology Commission [Z151100003915072] Key Research Program of the Chinese Academy of Sciences [KJZDEW-TZ-L05] Thousand Young Talents Program of China State Key Laboratory of Stem Cell and Reproductive Biology [2016SRLabKF13] UCAM G. Harold and LeilaY. Mathers Charitable Foundation Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002] Moxie Foundation 

主　　题：ALS CRISPR/Cas9 gene correction,iPSC disease modeling 

摘      要：Amyotrophic lateral sclerosis （ALS） is a complex neu- rodegenerative 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＋1A27~c and FUS＋/GISe6A mutations, respectively. We further gener- ated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing （RNA-seq） analysis of motor neurons derived from SOD1＋~A272c 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.