Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/86517
Title: Reversal of Phenotypic Abnormalities by CRISPR/Cas9-Mediated Gene Correction in Huntington Disease Patient-Derived Induced Pluripotent Stem Cells
Authors: Augustine, George James
Pouladi, Mahmoud A.
Xu, Xiaohong
Tay, Yilin
Sim, Bernice
Yoon, Su-In
Huang, Yihui
Ooi, Jolene
Utami, Kagistia Hana
Ziaei, Amin
Ng, Bryan
Radulescu, Carola
Low, Donovan
Ng, Alvin Yu Jin
Loh, Marie
Venkatesh, Byrappa
Ginhoux, Florent
Keywords: CHCHD2
hiPSC
Issue Date: 2017
Source: Xu, X., Tay, Y., Sim, B., Yoon, S.-I., Huang, Y., Ooi, J., et al. (2017). Reversal of Phenotypic Abnormalities by CRISPR/Cas9-Mediated Gene Correction in Huntington Disease Patient-Derived Induced Pluripotent Stem Cells. Stem Cell Reports, 8(3), 619-633.
Series/Report no.: Stem Cell Reports
Abstract: Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. Here we report correction of HD human induced pluripotent stem cells (hiPSCs) using a CRISPR-Cas9 and piggyBac transposon-based approach. We show that both HD and corrected isogenic hiPSCs can be differentiated into excitable, synaptically active forebrain neurons. We further demonstrate that phenotypic abnormalities in HD hiPSC-derived neural cells, including impaired neural rosette formation, increased susceptibility to growth factor withdrawal, and deficits in mitochondrial respiration, are rescued in isogenic controls. Importantly, using genome-wide expression analysis, we show that a number of apparent gene expression differences detected between HD and non-related healthy control lines are absent between HD and corrected lines, suggesting that these differences are likely related to genetic background rather than HD-specific effects. Our study demonstrates correction of HD hiPSCs and associated phenotypic abnormalities, and the importance of isogenic controls for disease modeling using hiPSCs.
URI: https://hdl.handle.net/10356/86517
http://hdl.handle.net/10220/44036
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2017.01.022
Rights: © 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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