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 journalArticle

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Abstract

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
Volume446
Issue number3
DOIs
Publication statusPublished - 2012 Sep 15

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Induced Pluripotent Stem Cells
Huntington Disease
Stem cells
Proteomics
Proteins
Oxidative stress
Oxidative Stress
Transcription Factor 3
Peroxiredoxins
Biological Phenomena
Ataxia Telangiectasia
Inborn Genetic Diseases
Cytoskeleton
Neurodegenerative Diseases
Cell death
Cell Death
Superoxide Dismutase
Cell Line

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chae, Jung Il ; Kim, Dong Wook ; Lee, Nayeon ; Jeon, Young Joo ; Jeon, Iksoo ; Kwon, Jihye ; Kim, Jumi ; Soh, Yunjo ; Lee, Dong Seok ; Seo, Kang Seok ; Choi, Nag Jin ; Park, Byoung Chul ; Kang, Sung Hyun ; Ryu, Joohyun ; Oh, Seung Hun ; Shin, Dong Ah ; Lee, Dong Ryul ; Do, Jeong Tae ; Park, In Hyun ; Daley, George Q. ; Song, Jihwan. / Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient. In: Biochemical Journal. 2012 ; Vol. 446, No. 3. pp. 359-371.
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abstract = "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.",
author = "Chae, {Jung Il} and Kim, {Dong Wook} and Nayeon Lee and Jeon, {Young Joo} and Iksoo Jeon and Jihye Kwon and Jumi Kim and Yunjo Soh and Lee, {Dong Seok} and Seo, {Kang Seok} and Choi, {Nag Jin} and Park, {Byoung Chul} and Kang, {Sung Hyun} and Joohyun Ryu and Oh, {Seung Hun} and Shin, {Dong Ah} and Lee, {Dong Ryul} and Do, {Jeong Tae} and Park, {In Hyun} and Daley, {George Q.} and Jihwan Song",
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Chae, JI, Kim, DW, Lee, N, Jeon, YJ, Jeon, I, Kwon, J, Kim, J, Soh, Y, Lee, DS, Seo, KS, Choi, NJ, Park, BC, Kang, SH, Ryu, J, Oh, SH, Shin, DA, Lee, DR, Do, JT, Park, IH, Daley, GQ & Song, J 2012, 'Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient', Biochemical Journal, vol. 446, no. 3, pp. 359-371. https://doi.org/10.1042/BJ20111495

Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient. / Chae, Jung Il; Kim, Dong Wook; Lee, Nayeon; Jeon, Young Joo; Jeon, Iksoo; Kwon, Jihye; Kim, Jumi; Soh, Yunjo; Lee, Dong Seok; Seo, Kang Seok; Choi, Nag Jin; Park, Byoung Chul; Kang, Sung Hyun; Ryu, Joohyun; Oh, Seung Hun; Shin, Dong Ah; Lee, Dong Ryul; Do, Jeong Tae; Park, In Hyun; Daley, George Q.; Song, Jihwan.

In: Biochemical Journal, Vol. 446, No. 3, 15.09.2012, p. 359-371.

Research output: Contribution to journalArticle

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T1 - Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient

AU - Chae, Jung Il

AU - Kim, Dong Wook

AU - Lee, Nayeon

AU - Jeon, Young Joo

AU - Jeon, Iksoo

AU - Kwon, Jihye

AU - Kim, Jumi

AU - Soh, Yunjo

AU - Lee, Dong Seok

AU - Seo, Kang Seok

AU - Choi, Nag Jin

AU - Park, Byoung Chul

AU - Kang, Sung Hyun

AU - Ryu, Joohyun

AU - Oh, Seung Hun

AU - Shin, Dong Ah

AU - Lee, Dong Ryul

AU - Do, Jeong Tae

AU - Park, In Hyun

AU - Daley, George Q.

AU - Song, Jihwan

PY - 2012/9/15

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N2 - 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.

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