4.6 Article

Reversal of Phenotypic Abnormalities by CRISPR/Cas9-Mediated Gene Correction in Huntington Disease Patient-Derived Induced Pluripotent Stem Cells

期刊

STEM CELL REPORTS
卷 8, 期 3, 页码 619-633

出版社

CELL PRESS
DOI: 10.1016/j.stemcr.2017.01.022

关键词

-

资金

  1. Strategic Positioning Fund for Genetic Orphan Diseases [SPF2012/005]
  2. Agency for Science, Technology and Research (Singapore) [1431AFG122]
  3. Tier 1 grant from Ministry of Education (Singapore) [R-172-000-297-112]
  4. Singapore Immunology Network (SIgN) core funding
  5. A*STAR Research Attachment Program (ARAP)
  6. A*STAR Singapore International Graduate Award (SINGA)

向作者/读者索取更多资源

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 HDand 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 betweenHDand 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据