| Project/Area Number |
26501003
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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 |
Regenerative medicine
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
李 佩俐 鳥取大学, 医学(系)研究科(研究院), 助教 (40464292)
森川 久未 鳥取大学, 医学部附属病院, 助教 (90707217)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ヒトES細胞 / ヒトiPS細胞 / イオンチャネル / 蛍光タンパク質 / 心筋分化 / 再生医療 / ペースメーカ細部 / ペースメーカ細胞 / iPS細胞 / 可視化 / 心筋分化誘導 / HCN4 / MLC2v / CRISPR/Cas9 / 心筋細胞 / HCN4イオンチャネル |
|---|
| Outline of Final Research Achievements |
In order to use human ES/iPS cells in the fields of regenerative medicine and drug development, it is crucial to identify functionally distinct cardiac subtypes and to study their functional aspects in healthy and diseased conditions. To isolate nodal pacemaker cells and ventricular cardiomyocytes, we have established the dual cardiac fluorescent reporter human ES/iPS cells, in which HCN4 ion channel and MLC2v myosin light chain genes are knocked in with eGFP and mCherry, respectively.
Isolated HCN4-eGFP-positive (HCN4+) cells expressed endogenous HCN4 and exhibited action potential characteristic of a nodal-phenotype including If current. Using imaging techniques, we demonstrated that HCN4+ cells established electrical coupling with HL-1 atrial CMs. These results demonstrated the potential of human ES/iPS cells-derived HCN4+ cells to act as a rate-responsive biological pacemaker.
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