Investigating the molecular mechanism of cardiomyocyte dedifferentiation induced by a novel transcription factor

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Ogawa Masahito 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (00898009)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 再生 / 心筋細胞 / 増殖 / 脱分化 / ゼブラフィッシュ

Outline of Final Research Achievements

Here, we identified a transcription factor (TF) that possesses a novel role in cardiomyocyte (CM) dedifferentiation and could know how the TF can cause the phenomenon. CM dedifferentiation and proliferation, the key events to achieve cardiac regeneration in zebrafish were controlled by distinct genetic pathways. The genetically modified zebrafish models can specifically promote or impede CM dedifferentiation through the loss of and gain of function of the TF demonstrating the important role of dedifferentiation during cardiac regeneration. Epigenomic approaches highlighted the induction mechanism of CM dedifferentiation caused by the TF.

Free Research Field

循環器

Academic Significance and Societal Importance of the Research Achievements

これまで心臓再生時において心筋脱分化が観察されており再生機構に重要であると考えられてきたが、その機能はまだ詳しく理解されていない。本研究は心筋脱分化の重要性を明らかにする事に成功した。これにより心筋自己再生を応用した再生療法を開発するために重要な制御機構の解明になると言え、新たな心不全治療の確立に役立つと考えられる。