Identification of master factors for mesoderm induction from pluripotent stem cells and establishment of a method for selective cardiac induction
| Project/Area Number |
18K08114
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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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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 再生 / 多能性幹細胞 / 中胚葉 / 発生 / 心筋再生 / 心臓中胚葉 / ダイレクトリプログラミング / 心筋細胞 / メカノトランスダクション / 細胞増殖 / 骨格筋 / 軟骨細胞 / 心臓 |
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| Outline of Final Research Achievements |
In order to induce cardiomyocytes from pluripotent stem cells, it is common to use multiple growth factors to induce cardiac mesoderm and then differentiate it into cardiomyocytes. However, this method suffers from the complexity of the induction process and the high cost of growth factors. We have discovered that cardiac mesoderm cells can be induced from pluripotent stem cells, such as mouse ES cells and human iPS cells, without the use of growth factors by overexpression of Tbx6. Furthermore, we found that skeletal muscle and chondrocytes can be induced by adjusting the expression period of Tbx6. We also found that the Tbx6 gene has a proliferative effect on cardiomyocytes, indicating the possibility of a new cardiac regeneration therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
世界総死亡数のなかで、心疾患は約半数を占める。終末分化細胞である心筋細胞には増殖能がなく、一度低下した心臓機能が回復することは困難である。ES細胞、iPS細胞などの幹細胞から、心臓幹細胞である心臓中胚葉を経て分化した誘導心筋は、再生医療のツールとして期待されるが、液性因子による誘導が必須である。この誘導法は、高価な液性因子によるコストの問題以外に、誘導手法が不安定かつ煩雑という課題がある。液性因子に頼らず、単一遺伝子によって多能性幹細胞から選択的な心臓中胚葉・心筋細胞への誘導が可能となる本研究成果により安定かつ簡便、さらに安価に心筋作製が可能となり、心臓再生医療の飛躍的な前進が期待される。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] 2.Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts.2019
Author(s)
Haginiwa S, Sadahiro T, Kojima H, Isomi M, Tamura F, Kurotsu S, Tani H, Muraoka N, Miyake N, Miyake K, Fukuda K, Ieda M.
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Journal Title
Biochem Biophys Res Commun
Volume: 513
Issue: 4
Pages: 1041-1047
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification.2018
Author(s)
Sadahiro T, Isomi M, Muraoka N, Kojima H, Haginiwa S, Kurotsu S, Tamura F, Tani H, Tohyama S, Fujita J, Miyoshi H, Kawamura Y, Goshima N, Iwasaki YW, Murano K, Saito K, Oda M, Andersen P, Kwon C, Uosaki H, Nishizono H, Fukuda K, Ieda M
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Journal Title
Cell stem cell
Volume: 23(3)
Issue: 3
Pages: 382-395
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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