Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient

Jung Il Chae, Dong Wook Kim, Nayeon Lee, Young Joo Jeon, Iksoo Jeon, Jihye Kwon, Jumi Kim, Yunjo Soh, Dong Seok Lee, Kang Seok Seo, Nag Jin Choi, Byoung Chul Park, Sung Hyun Kang, Joohyun Ryu, Seung Hun Oh, Dong Ah Shin, Dong Ryul Lee, Jeong Tae Do, In Hyun Park, George Q. DaleyJihwan Song

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)


HD (Huntington's disease) is a devastating neurodegenerative genetic disorder caused by abnormal expansion of CAG repeats in the HTT (huntingtin) gene.We have recently established two iPSC (induced pluripotent stem cell) lines derived from a HD patient carrying 72 CAG repeats (HD-iPSC). In order to understand the proteomic profiles of HD-iPSCs, we have performed comparative proteomic analysis among normal hESCs (human embryonic stem cells; H9), iPSCs (551-8) and HD-iPSCs at undifferentiated stages, and identified 26 up- and down-regulated proteins. Interestingly, these differentially expressed proteins are known to be involved in different biological processes, such as oxidative stress, programmed cell death and cellular oxygenassociated proteins. Among them, we found that oxidative stressrelated proteins, such as SOD1 (superoxide dismutase 1) and Prx (peroxiredoxin) families are particularly affected in HD-iPSCs, implying that HD-iPSCs are highly susceptible to oxidative stress. We also found that BTF3 (basic transcription factor 3) is upregulated in HD-iPSCs, which leads to the induction of ATM (ataxia telangiectasia mutated), followed by activation of the p53- mediated apoptotic pathway. In addition, we observed that the expression of cytoskeleton-associated proteins was significantly reduced in HD-iPSCs, implying that neuronal differentiation was also affected. Taken together, these results demonstrate that HDiPSCs can provide a unique cellular disease model system to understand the pathogenesis and neurodegeneration mechanisms in HD, and the identified proteins from the present study may serve as potential targets for developing future HD therapeutics.

Original languageEnglish
Pages (from-to)359-371
Number of pages13
JournalBiochemical Journal
Issue number3
Publication statusPublished - 2012 Sept 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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