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

SCOPUSTM   
Citations 5

134
Updated on Jan 14, 2023

Web of ScienceTM
Citations 5

132
Updated on Jan 27, 2023

Page view(s) 20

562
Updated on Jan 28, 2023

Download(s) 20

170
Updated on Jan 28, 2023

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.