| Project/Area Number |
17K08490
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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 |
General anatomy (including histology/embryology)
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| Research Institution | Kyoto Prefectural University of Medicine (2019)
Osaka University (2017) |
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Principal Investigator |
Saba Rie 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80378893)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 心臓発生 / 心内膜 / 心筋 / シングルセル解析 / 発生・分化 / 細胞・組織 / 発現制御 / 解剖学 / 再生医学 |
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| Outline of Final Research Achievements |
The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Our single cell cDNA expression profiling of cardiac progenitor cells (CPCs) shows that Nkx2-5+ CPCs expressing Sox17 specifically differentiate into the endocardium in mouse embryos. The expression of Sox17 is highly correlated to the endothelial markers, such as Dll4 and Pecam1, but not to the cardiomyocyte or smooth cell markers. Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, it is required for heart development. Deletion of Sox17 in the mesoderm markedly impaired heart development with regard to cell proliferation and behavior in both of the endocardium and myocardium. Our results provide insight into differentiation of the endocardium and its role in heart development. Above results were published in 2019 (Saba et al., Scientific Reports (2019) 9:11953).
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| Academic Significance and Societal Importance of the Research Achievements |
心内膜は、発生過程で心筋と同時に出現し、心筋細胞の分化増殖を制御する必須な役割を果たしながら心臓形成に細胞ソースとして寄与するが、その分化過程や機能の分子メカニズムについては不明な点が多かった。本研究で報告者は、マウス胚予定心臓領域で心内膜前駆細胞群が転写因子 SOX17 を発現することを発見した。また心内膜前駆細胞群におけるその欠損が、心室心筋層肥厚過程において細胞分化および増殖低下による肉柱形成不全をもたらすことを明らかにした。報告者は、心内膜派生過程と心筋層肥厚過程を制御する分子メカニズムの一端を明らかにした本研究成果が、重症心疾患治療のための新規細胞治療法開発の一助となると考えている。
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