Generation of corrected-hiPSC (USTCi001-A-1) from epilepsy patient iPSCs using TALEN-mediated editing of the SCN1A gene

Huifang Zhao; Lang He; Shuai Li; Hualin Huang; Feng Tang; Xiaobo Han; Zuoxian Lin; Chao Tian; Rongqi Huang; Peng Zhou; Jufang Huang; Sihao Deng; Zhiyuan Li

doi:10.1016/j.scr.2020.101864

Generation of corrected-hiPSC (USTCi001-A-1) from epilepsy patient iPSCs using TALEN-mediated editing of the SCN1A gene

Stem Cell Res. 2020 Jul:46:101864. doi: 10.1016/j.scr.2020.101864. Epub 2020 Jun 9.

Authors

Huifang Zhao¹, Lang He², Shuai Li³, Hualin Huang³, Feng Tang³, Xiaobo Han³, Zuoxian Lin⁴, Chao Tian¹, Rongqi Huang³, Peng Zhou⁵, Jufang Huang⁵, Sihao Deng⁵, Zhiyuan Li⁶

Affiliations

¹ School of Life Sciences, University of Science and Technology of China, Hefei, China; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 510005 Guangzhou, China.
² Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 510005 Guangzhou, China.
⁴ CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 510005 Guangzhou, China.
⁵ Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
⁶ School of Life Sciences, University of Science and Technology of China, Hefei, China; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, China; Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 510005 Guangzhou, China. Electronic address: li_zhiyuan@gibh.ac.cn.

PMID: 32544858
DOI: 10.1016/j.scr.2020.101864

Abstract

Dravet syndrome is a neurological disorder characterized by treatment-resistant polymorphic seizures, primarily caused by loss-of-function in the SCN1A gene. To develop an in vitro model of this disease, in a previously study we generated an induced pluripotent stem cell line from a 10-year-old boy carrying the NM_001165963.1:c.5768A to G (Q1923R) mutation in SCN1A. Using TALEN-mediated genome editing, we have now generated an isogenic control line in which the disease-causing mutation found in the epilepsy patient iPSCs was corrected, in order to eliminate the interference of different genetic backgrounds in future analyses.

Keywords: Dravet syndrome; TALEN; iPSC.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Child
Epilepsies, Myoclonic* / genetics
Epilepsy* / genetics
Humans
Induced Pluripotent Stem Cells*
Male
NAV1.1 Voltage-Gated Sodium Channel / genetics
Transcription Activator-Like Effector Nucleases / genetics

Substances

NAV1.1 Voltage-Gated Sodium Channel
SCN1A protein, human
Transcription Activator-Like Effector Nucleases