Abstract
Cardiomyocyte (CM) maturation, which is characterized by structural, functional, and metabolic specializations, is the last phase of CM development that prepares the cells for efficient and forceful contraction throughout life. Over the past decades, CM maturation has gained increased attention due to the fact that pluripotent stem cell-derived CMs are structurally, transcriptionally, and functionally immature and embryonic-like, which causes a defect in cell replacement therapy. The current challenge is to discover and understand the molecular mechanisms, which control the CM maturation process. Currently, emerging shreds of evidence emphasize the role of long noncoding RNAs (lncRNAs) in regulating different aspects of CM maturation, including myofibril maturation, electrophysiology, and Ca2+ handling maturation, metabolic maturation and proliferation to hypertrophy transition. Here, we describe the structural and functional characteristics of mature CMs. Furthermore, this review highlights the lncRNAs as crucial regulators of different aspects in CM maturation, which have the potential to be used for mature CM production. With the current advances in oligonucleotide delivery; lncRNAs may serve as putative therapeutic targets to produce highly mature CMs for research and regenerative medicine.
Highlights
Cardiac Regenerative Medicine.Directed differentiation of human pluripotent stem cells to cardiomyocytes (CMs) has achieved remarkable progress over the past decade
Several long noncoding RNAs (lncRNAs) are expressed during the heart development and of interest cardiomyocyte maturation
LncRNAs are defined to regulate the maturation in different aspects, including myofibril maturation, electrophysiology and Ca2+ handling maturation, metabolic maturation and proliferation to hypertrophy transition
Summary
Directed differentiation of human pluripotent stem cells (hPSCs) to cardiomyocytes (CMs) has achieved remarkable progress over the past decade. These have provided powerful resources to study human development, translational research to discover disease mechanisms, new drug discovery as well as cell replacement therapy [1]. The current challenge is to discover and understand the molecular mechanisms, which control the CM maturation process. Cardiomyocyte maturation is the last phase of heart development characterized by structural, gene expression, metabolic, and functional specializations. A large number of lncRNAs are cardiac-specific or dynamically expressed during the differentiation and maturation processes. We introduce the most novel and important maturation-related lncRNAs and describe their corresponding molecular mechanism in regulating the CM maturation process
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