Induction of cardiac mesoderm by defined factors
| Project/Area Number |
17H04179
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | University of Tsukuba (2018-2019, 2021)
Keio University (2017) |
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Principal Investigator |
Ieda Masaki 筑波大学, 医学医療系, 教授 (70296557)
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| Co-Investigator(Kenkyū-buntansha) |
五島 直樹 国立研究開発法人産業技術総合研究所, 生命工学領域, 招聘研究員 (70215482)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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| Keywords | 心臓再生 / リプログラミング / 心臓前駆細胞 / 再生 / 心臓 / 分子心臓学 |
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| Outline of Final Research Achievements |
Adult hearts have little regenerative capacity. We found that Tbx6 overexpression could induce mesoderm and cardiac progenitor gene expression in fibroblasts. We also found that Tbx6 is critical for mesoderm induction and subsequent lineage diversification from pluripotent stem cells (PSCs). Transient Tbx6 expression induced nascent mesoderm and cardiovascular lineages from mouse and human PSCs, whereas prolonged Tbx6 expression suppressed cardiac differentiation and induced somite lineages, including skeletal muscle and chondrocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は線維芽細胞を直接心臓前駆細胞に転換して心臓再生する全く新しい概念の研究である。これまで自らが積み上げてきた心筋直接リプログラミング研究の多くの知見や材料を利用するため、他より圧倒的に優位な立場で研究を進められる。線維芽細胞から心臓前駆細胞へのリプログラミングは、他の様々な臓器でも組織幹細胞への直接リプログラミングが可能であることを示しており、心臓再生医療実現への貢献のみならず他領域への大きな波及効果も期待できる。
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Report
(4 results)
Research Products
(24 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] Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction.2018
Author(s)
Miyamoto K, Akiyama M, Tamura F, Isomi M, Yamakawa H, Sadahiro T, Muraoka N, Kojima H, Haginiwa S, Kurotsu S, Tani H, Wang L, Qian L, Inoue M, Ide Y, Kurokawa J, Yamamoto T, Seki T, Aeba R, Yamagishi H, Fukuda K, Ieda M.
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Journal Title
Cell Stem Cell.
Volume: 4
Issue: 1
Pages: 91-103
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Single-Construct Polycistronic Doxycycline-Inducible Vectors Improve Direct Cardiac Reprogramming and Can Be Used to Identify the Critical Timing of Transgene Expression.2017
Author(s)
Umei TC, Yamakawa H, Muraoka N, Sadahiro T, Isomi M, Haginiwa S, Kojima H, Kurotsu S, Tamura F, Osakabe R, Tani H, Nara K, Miyoshi H, Fukuda K, Ieda M.
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Journal Title
Int J Mol Sci.
Volume: 18
Issue: 8
Pages: 1805-1805
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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