Heart Development and Regeneration via Cellular Interaction and Reprogramming
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概要
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The heart consists of many types of cells, including cardiomyocytes, vascular cells, neural cells, and cardiac fibroblasts. Adult cardiomyocytes are terminally differentiated cells, and loss of cardiomyocytes as a result of heart damage is irreversible. To regenerate damaged hearts and restore cardiac function, understanding the cellular and molecular basis of heart development is of considerable importance. Although it is well known that heart function is tightly regulated by cell–cell interactions, their roles in heart development are not clear. Recent studies, including ours, identified important roles of cell–cell interactions in heart development and function. The balance between neural chemoattractants and chemorepellents secreted from cardiomyocytes determines cardiac nervous development. Nerve growth factor is a potent chemoattractant synthesized by cardiomyocytes, whereas Sema3a is a neural chemorepellent expressed specifically in the subendocardium. Disruption of this molecular balance induces disorganized cardiac innervation and may lead to sudden cardiac death due to lethal arrhythmias. Cardiac fibroblasts, of which there are large populations in the heart, secrete high levels of specific extracellular matrix and growth factors. Embryonic cardiac fibroblast-specific secreted factors collaboratively promote mitotic activity of embryonic cardiomyocytes and expansion of ventricular chambers during cardiogenesis. More recently, utilizing knowledge of the regulatory mechanisms of heart development, we found that cardiac fibroblasts can be directly reprogrammed into cardiomyocyte-like cells in vitro and in vivo by gene transfer of cardiac-specific transcription factors. Understanding the mechanisms of heart development and cardiac reprogramming technology may provide new therapeutic approaches for heart disease in the future.
著者
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Ieda Masaki
Department of Cardiology, Keio University School
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Ieda Masaki
Department of Clinical and Molecular Cardiovascular Research, School of Medicine, Keio University, Tokyo, Japan
関連論文
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- Molecular Characterization and Pluripotency of the Cardiac Side Population Cells(Development and Differentiation 2 (M), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- FRS-056 Heat-shock Protein 60 is Required for Cardiac Regeneration in Zebrafish(Regeneration, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
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- PE-571 Neural Crest Stem Cells Contribute to Adipose Tissue-derived Tissue Stem Cells and Can Differentiate into Cardiomyocytes(Regeneration (angiogenesis/myocardial regeneration)-4, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
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- FRS-058 Neural Crest-Derived Stem Cell in the Heart Proliferate and Differentiate into Cardiomyocytes after Myocardial Infarction(Regeneration, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- OE-301 Cardiac Neural Crest-Derived Cells Lay Hidden as Dormant Stem Cells and Differentiate into Cardiomyocytes in Vivo(Development and differentiation-1 (M) OE51,Oral Presentation (English),The 70th Anniversary Annual Scientific Meeting of the Japanese
- OE-355 Endothelin-1 Disruption Retards Cardiac Sympathetic Nerve Development by Down Regulation of Nerve Growth Factor(Development and Differentiation 2 (H) : OE45)(Oral Presentation (English))
- OE-083 Dominant Negative Suppression of Rad Prolongs QT Interval and Causes Ventricular Arrhythmias in Mice(Arrhythmia, basic-1, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
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- New Aspects for the Treatment of Cardiac Diseases Based on the Diversity of Functional Controls on Cardiac Muscles : The Regulatory Mechanisms of Cardiac Innervation and Their Critical Roles in Cardiac Performance
- Heart Development and Regeneration via Cellular Interaction and Reprogramming