Cardiac reprogramming and miRNA
| Project/Area Number |
26293193
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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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) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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| Keywords | 再生 / リプログラミング / マイクロRNA / 再生医学 / 循環器・高血圧 / 心筋 / miR |
|---|
| Outline of Final Research Achievements |
Here we found that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated 7-fold more beating iCMs from mouse embryonic fibroblasts, and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts.
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Report
(5 results)
Research Products
(47 results)
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[Journal Article] Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction2018
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
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 Expression2017
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
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 signaling.2017
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] Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1+CXCR5-/dim B-helper T cell induction.2017
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
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 Implantation2016
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
Circulation Heart Failure
Volume: 9
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
Pages: 350-357
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Book] 心臓2016
Author(s)
貞廣威太郎、家田真樹
Publisher
株式会社日本医学出版
Related Report
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[Book] 細胞2016
Author(s)
山川裕之、家田真樹
Publisher
株式会社ニューサイエンス
Related Report
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