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Neuronal Properties, In Vivo Effects, and Pathology of a Huntington's Disease Patient-Derived Induced Pluripotent Stem Cells

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Author

  • Iksoo Jeon
  • Nayeon Lee
  • Jia-Yi Li
  • In-Hyun Park
  • Kyoung Sun Park
  • Jisook Moon
  • Sung Han Shim
  • Chunggab Choi
  • Da-Jeong Chang
  • Jihye Kwon
  • Seung-Hun Oh
  • Dong Ah Shin
  • Hyun Sook Kim
  • Jeong Tae Do
  • Dong Ryul Lee
  • Manho Kim
  • Kyung-Sun Kang
  • George Q. Daley
  • Patrik Brundin
  • Jihwan Song
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Summary, in English

Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can be used to model different human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. Here, we analyzed neuronal properties of an iPSC line derived from a patient with a juvenile form of Huntington's disease (HD) carrying 72 CAG repeats (HD-iPSC). Although its initial neural inducing activity was lower than that of human embryonic stem cells, we found that HD-iPSC can give rise to GABAergic striatal neurons, the neuronal cell type that is most susceptible to degeneration in HD. We then transplanted HD-iPSC-derived neural precursors into a rat model of HD with a unilateral excitotoxic striatal lesion and observed a significant behavioral recovery in the grafted rats. Interestingly, during our in vitro culture and when the grafts were examined at 12 weeks after transplantation, no aggregate formation was detected. However, when the culture was treated with a proteasome inhibitor (MG132) or when the cells engrafted into neonatal brains were analyzed at 33 weeks, there were clear signs of HD pathology. Taken together, these results indicate that, although HD-iPSC carrying 72 CAG repeats can form GABAergic neurons and give rise to functional effects in vivo, without showing an overt HD phenotype, it is highly susceptible to proteasome inhibition and develops HD pathology at later stages of transplantation. These unique features of HD-iPSC will serve as useful tools to study HD pathology and develop novel therapeutics. Stem Cells 2012; 30: 20542062

Publishing year

2012

Language

English

Pages

2054-2062

Publication/Series

Stem Cells

Volume

30

Issue

9

Document type

Journal article

Publisher

AlphaMed Press

Topic

  • Cell and Molecular Biology

Keywords

  • Huntington's disease
  • Induced pluripotent stem cells
  • GABAergic neurons
  • Quinolinic acid
  • Behavioral recovery
  • Aggregate formation

Status

Published

Research group

  • Neural Plasticity and Repair

ISBN/ISSN/Other

  • ISSN: 1549-4918