CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs.
10.1007/s13238-017-0397-3
- Author:
Lixia WANG
1
;
Fei YI
2
;
Lina FU
1
;
Jiping YANG
1
;
Si WANG
1
;
Zhaoxia WANG
3
;
Keiichiro SUZUKI
4
;
Liang SUN
5
;
Xiuling XU
1
;
Yang YU
6
;
Jie QIAO
6
;
Juan Carlos Izpisua BELMONTE
4
;
Ze YANG
5
;
Yun YUAN
7
;
Jing QU
8
;
Guang-Hui LIU
9
Author Information
1. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
3. Department of Neurology, Peking University First Hospital, Beijing, 100034, China.
4. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.
5. Beijing Hospital of the Ministry of Health, Beijing, 100730, China.
6. Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
7. Department of Neurology, Peking University First Hospital, Beijing, 100034, China. yuanyun2002@126.com.
8. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
9. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
ALS;
CRISPR/Cas9;
gene correction;
iPSC disease modeling
- MeSH:
Amyotrophic Lateral Sclerosis;
genetics;
metabolism;
therapy;
Cell Line;
Clustered Regularly Interspaced Short Palindromic Repeats;
Genetic Therapy;
Genome-Wide Association Study;
Humans;
Induced Pluripotent Stem Cells;
metabolism;
Mutation, Missense;
RNA-Binding Protein FUS;
genetics;
metabolism;
Superoxide Dismutase-1;
genetics;
metabolism
- From:
Protein & Cell
2017;8(5):365-378
- CountryChina
- Language:English
-
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 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.
