About this Research Topic
Heart failure, the leading cause of global mortality, is often the unavoidable and irreversible consequence of cardiac injuries such as myocardial infarction, due to the little renewal capacity of adult mammalian cardiomyocytes (CM). In contrast, adult fish, amphibians, reptiles, and neonatal rodents have fully regenerative hearts. Studies in zebrafish and mice have uncovered conserved molecular mechanisms that can promote CM proliferation, such as Neuregulin, as well as barriers that block CMs from re-entering the cell cycles, such as polyploidization, the Hippo signaling pathway and thyroid hormone signaling. On the other hand, transcription factors (TFs) such as Mef2c, Gata4, Tbx5, Hand2 and others, are essential in CM fate determination and differentiation during development. These important TFs are capable of driving CM transcription programs in other cell lineages.
In order to restore cardiac function, researchers in regenerative medicine have developed diverse approaches to regrow CM. These include promoting non-proliferative CMs re-entering the cell cycle, trans-differentiating non-myocytes to CM, or transplanting induced CMs. However, all these methods are facing the significant barrier that the achieved CMs seem to possess immature features in sarcomere structure, contractility, metabolism and electrophysiology which may prevent them from potential therapeutic use.
CM maturation is a complex cellular process controlled by various molecular mechanisms that are often interconnected. This Research Topic will cover cutting-edge research into cardiomyocyte maturation. The areas of interest may include:
- technological platforms that allow quantitative analysis of CM maturation phenotypes.
- high-throughput platforms for genetic or small molecule screening.
- signaling pathways that control CM maturation (cell-autonomous and non-autonomous)
- evaluating the efficacy of in vivo cell therapies
- single-cell level transcriptomic and epigenetic analysis of cardiomyocyte subtypes
Keywords: Cardiomyocyte, Heart, Regeneration, Signaling Pathway, Reprogramming
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