2012 Fiscal Year Final Research Report
Understanding the functional mechanisms of cardiac cell induction
| Project/Area Number |
22689026
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKEUCHI Jun 東京大学, 分子細胞生物学研究所, 准教授 (10451999)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 心筋分化 / 心臓前駆細胞 / エピジェネティクス / クロマチン因子 |
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| Research Abstract |
Two types of cardiomyocytes; atria-ventricular cardiomyocytes are formed from their common progenitor cell lineages, but a key factor for induction of cardiac progenitor cells as well as the specification of cardiomyocytes is not known yet. To understand atria-ventricular cardiomyocyte or cardiac progenitor specification, we generated gene profiles from aMHC-GFP positive heart cells in these mice lines or Islet1/Flk positive cells in miceembryos. 6 genes were isolated as candidate factors for specification of atria-ventricular cardiomyocytes, 8 genes were screened out as cardiac progenitor specific-genes. Two genes, C or D, were expressed in undifferentiated cell region that defined by islet1/Nkx2-5 gene as major cardiac progenitor markers during development but not expressed in the heart forming region. These genes’ knockout mice exhibit severe defect of OFT and RV and die at approximately E9.5, suggesting that C/D-derived cells contribute to the heart and are essential for cardiogenesis. By using tamoxifen inducible creERT2-ROSA-YFP reporter system, lineage-tracing analysis of C/D-derived cells could easily demonstrated in vivo. In these analyses showed us that previously expressed these genes substantially contribute to the whole-heart in development, expressing in atria/ventricular cardiomyocytes, endothelial cells, smooth muscle, and conduction cells including pacemaker cells. In conclusion, re-expression of C/D as candidate genes is necessary to promote cardiac program in postnatal stages, suggesting that C/D genes play as key regulators to trigger cardiacprogram.
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[Journal Article] Chromatin Remodeling Complex Dosage Modulates Transcription Factor Function in Heart Development2011
Author(s)
Takeuchi JK, Lou X, Alexander JM, Sugizaki H, Delgado-Olguin P, Holloway AK, Mori A, Wylie JN, Munson C, Zhu Y, Yu-Qing Zhou9, Ru-Fang Yeh6, Henkelman RM, Harvey RP, Metzger D, Chambon P, Stainier DYR, Pollard KS, Scott IC, & Bruneau BG
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Journal Title
Nature Communications
Volume: 1187
Pages: 1-11
Peer Reviewed
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