期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 152, 期 -, 页码 80-91出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2020.11.016
关键词
Cardiomyocyte dedifferentiation; Development; Heart failure; Cell states; Epigenetics
资金
- National Medical Research Council
- Biomedical Research Council (ASTAR), Singapore
- President's Graduate Fellowship, National University of Singapore
The article discusses the importance of cardiomyocyte dedifferentiation in cardiac regeneration and the challenges in studying it. Despite some genes being proven to promote endogenous CM proliferation and the belief that CM dedifferentiation precedes cell division, there are still knowledge gaps and controversies surrounding the definition of CM dedifferentiation.
Cardiomyocytes (CMs) lost during cardiac injury and heart failure (HF) cannot be replaced due to their limited proliferative capacity. Regenerating the failing heart by promoting CM cell-cycle re-entry is an ambitious solution, currently vigorously pursued. Some genes have been proven to promote endogenous CM proliferation, believed to be preceded by CM dedifferentiation, wherein terminally differentiated CMs are initially reversed back to the less mature state which precedes cell division. However, very little else is known about CM dedifferentiation which remains poorly defined. We lack robust molecular markers and proper understanding of the mechanisms driving dedifferentiation. Even the term dedifferentiation is debated because there is no objective evidence of pluripotency, and could rather reflect CM plasticity instead. Nonetheless, the significance of CM transition states on cardiac function, and whether they necessarily lead to CM proliferation, remains unclear. This review summarises the current state of knowledge of both natural and experimentally induced CM dedifferentiation in non-mammalian vertebrates (primarily the zebrafish) and mammals, as well as the phenotypes and molecular mechanisms involved. The significance and potential challenges of studying CM dedifferentiation are also discussed. In summary, CM dedifferentiation, essential for CM plasticity, may have an important role in heart regeneration, thereby contributing to the prevention and treatment of heart disease. More attention is needed in this field to overcome the technical limitations and knowledge gaps.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据