Targeted gene correction minimally impacts whole-genome mutational load in human-disease-specific induced pluripotent stem cell clones

Suzuki, Keiichiro, Yu, Chang, Qu, Jing, Li, Mo, Yao, Xiaotian, Yuan, Tingting, Goebl, April, Tang, Senwei, Ren, Ruotong, Aizawa, Emi, Zhang, Fan, Xu, Xiuling, Soligalla, Rupa Devi, Chen, Feng, Kim, Jessica, Kim, Na Young, Liao, Hsin-Kai, Benner, Chris, Esteban, Concepcion Rodriguez, Jin, Yabin, Liu, Guang-Hui, Li, Yingrui and Belmonte, Juan Carlos Izpisua (2014) Targeted gene correction minimally impacts whole-genome mutational load in human-disease-specific induced pluripotent stem cell clones. Cell Stem Cell, 15 1: 31-36. doi:10.1016/j.stem.2014.06.016


Author Suzuki, Keiichiro
Yu, Chang
Qu, Jing
Li, Mo
Yao, Xiaotian
Yuan, Tingting
Goebl, April
Tang, Senwei
Ren, Ruotong
Aizawa, Emi
Zhang, Fan
Xu, Xiuling
Soligalla, Rupa Devi
Chen, Feng
Kim, Jessica
Kim, Na Young
Liao, Hsin-Kai
Benner, Chris
Esteban, Concepcion Rodriguez
Jin, Yabin
Liu, Guang-Hui
Li, Yingrui
Belmonte, Juan Carlos Izpisua
Title Targeted gene correction minimally impacts whole-genome mutational load in human-disease-specific induced pluripotent stem cell clones
Journal name Cell Stem Cell   Check publisher's open access policy
ISSN 1875-9777
1934-5909
Publication date 2014-07-03
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.stem.2014.06.016
Open Access Status DOI
Volume 15
Issue 1
Start page 31
End page 36
Total pages 6
Place of publication Cambridge, Massachusetts, United States
Publisher Cell Press
Language eng
Abstract The utility of genome editing technologies for disease modeling and developing cellular therapies has been extensively documented, but the impact of these technologies on mutational load at the whole-genome level remains unclear. We performed whole-genome sequencing to evaluate the mutational load at single-base resolution in individual gene-corrected human induced pluripotent stem cell (hiPSC) clones in three different disease models. In single-cell clones, gene correction by helper-dependent adenoviral vector (HDAdV) or Transcription Activator-Like Effector Nuclease (TALEN) exhibited few off-target effects and a low level of sequence variation, comparable to that accumulated in routine hiPSC culture. The sequence variants were randomly distributed and unique to individual clones. We also combined both technologies and developed a TALEN-HDAdV hybrid vector, which significantly increased gene-correction efficiency in hiPSCs. Therefore, with careful monitoring via whole-genome sequencing it is possible to apply genome editing to human pluripotent cells with minimal impact on genomic mutational load.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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