| Project/Area Number |
17K19523
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical structure and function and related fields
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| Research Institution | Kyoto Prefectural University of Medicine (2018-2019)
Osaka University (2017) |
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Principal Investigator |
Yashiro Kenta 京都府立医科大学, 医学(系)研究科(研究院), 教授 (60432506)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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| Keywords | 左心室心筋 / 右心室心筋 / 生物学的な相違 / 分化 / 左右心室心筋 / 相違 / 遺伝子発現プロファイル / 蛋白発現プロファイル / 力学特性 / Tbx5 / 循環器 / 発生・分化 / 解剖学 / プロテオーム |
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| Outline of Final Research Achievements |
Some clinical evidences strongly suggest that right ventricular cardiomyocytes are unable to support high pressure like systolic arterial pressure for long period. However, such an intrinsically different feature of right ventricular cardiomyocytes from those of left ventricle is still largely unknown. In this study, we have developed genetically modified (GM) mouse embryonic stem (ES) cell system (Bacterial Artificial Chromosome Tbx5CreERT2 transgene・ROSA26-eYFP) to discern right ventricular cardiomyocytes from left ventricular ones if differentiating in vitro. Then, we are about to isolate right ventricular cardiomyocytes and left ventricular ones originating from those ES cells in vitro, which will be then subjected to RNA-seq, phosphorylated protein profiling with mass spectrometry, and appreciation of mechanical property via calcium transient measurement. We will publish our results in international conference and scientific journal in the near future.
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| Academic Significance and Societal Importance of the Research Achievements |
右心室の心筋と左心室の心筋が本質的に異なるのであれば、まず、左右心室心筋に本質的な差がないことを前提とした右心不全の治療戦略を再考する必要性が生じる。また、現在のinduced pluripotent stem（iPS）/ES細胞を用いた再生医療用の心筋も、左右心室心筋が混在しているものであり、左室型心筋のみを抽出し使用する方が高品質である可能性が高い。残念ながら、本研究では期間内にデータ解析を完了できなかったが、研究の継続により近い将来に得られる最終成果は、上記の臨床戦略を再考すべきかどうかの医学的知見を提供し、生物学的にも極めて重要な疑問に迫ることができるはずである。
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