Epigenetic regulation of "differentiation timing" of cardiovascular cells
Project/Area Number |
23659415
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Circulatory organs internal medicine
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Research Institution | Kyoto University |
Principal Investigator |
YAMASHITA Jun 京都大学, 再生医科学研究所, 准教授 (50335288)
|
Project Period (FY) |
2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
|
Keywords | 幹細胞 / 分化 / エピジェネティクス / ヒストン修飾 / サイクリックAMP |
Research Abstract |
Velocity of cell differentiation is strictly controlled and is crucial for normal development and stem cell differentiation. However, underlying mechanisms regulating differentiation velocity are fully unknown. Here we show a molecular mechanism determining differentiation velocity from mouse embryonic stem cells(ESCs). Activation of protein kinase A(PKA) accelerates differentiation velocity to induce approximately 2-times earlier appearance of mesoderm and other germ layer cells, reciprocally correlated with the earlier disappearance of pluripotent markers after ESC differentiation. PKA activation increased protein expression of G9a, a H3K9 methyltransferase, along with earlier H3K9 dimethylation and DNA methylation in Oct3/4 and Nanog gene promoters. Deletion of G9a completely abolished PKA-elicited acceleration of differentiation and epigenetic modification. Furthermore, G9a knockout mice showed prolonged expressions of Oct3/4 and Nanog at embryonic day-7. 5 and delayed development.
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Report
(2 results)
Research Products
(46 results)
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[Journal Article] Pluripotent stem cell-engineered cell sheets re-assembled with defined cardiovascular populations ameliorate reduction in infarct heart function with cardiomyocyte-mediated neovascularization2012
Author(s)
Masumoto H, Matsuo T, Yamamizu K, Uosaki H, Narazaki G, Katayama S, Marui A, Shimizu T, Ikeda T, Okano T, Sakata R, Yamashita JK
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Journal Title
Stem Cells
Volume: 30
Issue: 6
Pages: 1196-1205
DOI
Related Report
Peer Reviewed
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[Journal Article] Effect of k-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells2012
Author(s)
Kuzumaki N, Suzuki A, Narita M, Hosoya T, Nagasawa A, Imai S, Yamamizu K, Morita H, Nagase H, Okada Y, Okano HJ, Yamashita JK, Okano H, Suzuki T, Narita M
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Journal Title
Br J Cancer
Volume: 106(Epub 2012 Feb 16)
Issue: 6
Pages: 1148-1152
DOI
Related Report
Peer Reviewed
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