2016 Fiscal Year Final Research Report
Myotonic dystrophy type 1 patient-derived iPSCs for the investigation of CTG repeat instability
| Project/Area Number |
26430053
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI Masanori 大阪大学, 大学院医学系研究科, 教授 (20359847)
NAKAMORI Masayuki 大阪大学, 大学院医学系研究科, 講師 (60630233)
WATANABE Akira 京都大学, iPS細胞研究所, 助教 (60506765)
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| Research Collaborator |
UEKI Junko
Jonouchi Tatsuya
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 病態再現 / 患者由来iPS細胞 / 筋強直性ジストロフィー / CTGリピート伸長 |
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| Outline of Final Research Achievements |
Myotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats in DMPK gene. The expanded CTG repeats are unstable and can increase the length of the gene with age, which worsens the symptoms. In order to investigate the repeat instability, DM1 patient-derived iPSCs were generated and differentiated into cardiomyocytes, neurons and myocytes, and we precisely analyzed the CTG repeat lengths of the cells. Our DM1-iPSCs showed a gradual lengthening of CTG repeats in all cell lines depending on the passage numbers of undifferentiated cells. However, the average CTG repeat length did not change significantly after differentiation into different somatic cell types. We also evaluated the chromatin accessibility in DM1-iPSCs using ATAC-seq. The chromatin status in DM1 cardiomyocytes was closed at the DMPK locus as well as at SIX5 and its promoter region, whereas it was open in control. These findings may help clarify the role of repeat instability in the CTG repeat expansion in DM1.
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| Free Research Field |
筋疾患学
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