title: CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs.
abstract: 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+/A272Cand FUS+/G1566Amutations, 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+/A272Cand 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.
authors.affiliation: 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.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Yi
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Fu
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Yang
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.|Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos, N 135 Guadalupe, 30107, Murcia, Spain.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Beijing Hospital of the Ministry of Health, Beijing, 100730, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Juan Carlos Izpisua
authors.initials: JCI
authors.lastname: Belmonte
authors.affiliation: Beijing Hospital of the Ministry of Health, Beijing, 100730, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, 100034, China. yuanyun2002@126.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.|University of Chinese Academy of Sciences, Beijing, 100049, China. qujing@ioz.ac.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Qu
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ibp.ac.cn.|University of Chinese Academy of Sciences, Beijing, 100049, China. ghliu@ibp.ac.cn.|Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, 510632, China. ghliu@ibp.ac.cn.|Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China. ghliu@ibp.ac.cn.
authors.forename: Guang-Hui
authors.identifier: 0000-0001-9289-8177
authors.initials: GH
authors.lastname: Liu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D002460:Cell Line; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D015316:Genetic Therapy; D055106:Genome-Wide Association Study; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D020125:Mutation, Missense; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1
keywords: ALS; CRISPR/Cas9; gene correction; iPSC disease modeling