Cardiac reprogramming and chemical compounds
| Project/Area Number |
15K15313
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Keio University |
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Principal Investigator |
Ieda Masaki 慶應義塾大学, 医学部(信濃町), 講師 (70296557)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 再生 / リプログラミング / 心筋 |
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| Outline of Final Research Achievements |
Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions. Here, we found that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 40-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4.
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Report
(4 results)
Research Products
(42 results)
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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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[Journal Article] Placental labyrinth formation in mice requires endothelial FLRT2/UNC5B signaling2017
Author(s)
Tai-Nagara Ikue、Yoshikawa Yusuke、Numata Naoko、Ando Tomofumi、Okabe Keisuke、Sugiura Yuki、Ieda Masaki、Takakura Nobuyuki、Nakagawa Osamu、Zhou Bin、Okabayashi Koji、Suematsu Makoto、Kitagawa Yuko、Bastmeyer Martin、Sato Kohji、Klein R?diger、Navankasattusas Sutip、Li Dean Y.、Yamagishi Satoru、Kubota Yoshiaki
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Journal Title
Development
Volume: 144
Pages: 2392-2401
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure2017
Author(s)
Ono T, Kamimura N, Matsuhashi T, Nagai T, Nishiyama T, Endo J, Hishiki T, Nakanishi T, Shimizu N, Tanaka H, Ohta S, Suematsu M, Ieda M, Sano M, Fukuda K, Kaneda R
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Journal Title
Sci Rep.
Volume: 7
Issue: 1
Pages: 39752-39752
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Effective Cibenzoline Treatment in a Patient With Midventricular Obstruction After Transcatheter Aortic Valve Implantation.2016
Author(s)
Isobe S, Ieda M, Kohno T, Nishiyama T, Maekawa Y, Tsuruta H, Murata M, Yashima F, Yanagisawa R, Tanaka M, Inami S, Nasuno T, Haruyama A, Sano M, Hayashida K, Fukuda K.
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Journal Title
Circ Heart Fail
Volume: 9
Issue: 1
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Neural crest-derived resident cardiac cells contribute to the restoration of adrenergic function of transplanted heart in rodent.2016
Author(s)
Tamura Y, Sano M, Nakamura H, Ito K, Sato Y, Shinmura K, Ieda M, Fujita J, Kurosawa H, Ogawa S, Nakano S, Matsuzaki M, Fukuda K.
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Journal Title
Cardiovasc Res.
Volume: 109
Issue: 3
Pages: 350-357
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Book] 心臓2016
Author(s)
家田真樹
Total Pages
333
Publisher
日本医学出版
Related Report
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