ArticleProceedings of the National Academy of Sciences of the United States of America2015
Let-7 family of microRNA is required for maturation and adult-like metabolism in stem cell-derived cardiomyocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.
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Who cites it
175 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023Pooled it
- Carbohydrate intake in recovery from aerobic exercise differentiates skeletal muscle microRNA expression.American journal of physiology. Endocrinology and metabolism · 2022Trial
- A study on extracellular and cellular composition to advance towards the rational design of contractile human myocardium.Materials today. Bio · 2026Article
- Metabolic fatty acid substrates enhance the structural and mechanical performance of human-induced pluripotent stem cell-derived cardiomyocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Review
- Epicardial extracellular vesicles modulate gene expression following ischemia-reperfusion injury in heart-on-a-chip.Materials today. Bio · 2026Article
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- Advanced physiological maturation of human iPSC-derived cardiomyocytes using an algorithm-directed optimization of defined media components.Nature communications · 2026Article
- Engineering Mitochondrial Biogenesis in iPSC-CMs: CRISPR-Guided Approaches for Advanced Cardiomyocyte Development.Journal of cardiovascular development and disease · 2026Review
- A model for the human fetal ventricular myocyte electrophysiology.PLoS computational biology · 2026Article
- Recent Advances of Pluripotent Stem Cell-Derived Cardiomyocytes for Regenerative Medicine.Metabolites · 2025Review
- Matured hiPSC-derived cardiomyocytes possess dematuration plasticity.Journal of molecular and cellular cardiology plus · 2025Article
- Let-7 Family as a Mediator of Exercise on Alzheimer's Disease.Cellular and molecular neurobiology · 2025Review
- Deciphering the roles of cellular and extracellular non-coding RNAs in chemotherapy-induced cardiotoxicity.Molecular and cellular biochemistry · 2025Review
- Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice.Stem cell research & therapy · 2025Article
- Petri net modeling and simulation of post-transcriptional regulatory networks of human embryonic stem cell (hESC) differentiation to cardiomyocytes.Journal of integrative bioinformatics · 2025Article
- Article
- Clinical translation of human iPSC technologies: advances, safety concerns, and future directions.Frontiers in cell and developmental biology · 2025Review
- Independent control of functional rewiring after axon injury byJournal of biosciences · 2025Article
- Transforming Cardiotoxicity Detection in Cancer Therapies: The Promise of MicroRNAs as Precision Biomarkers.International journal of molecular sciences · 2024Review
115 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors.
Funding
Abstract
In metazoans, transition from fetal to adult heart is accompanied by a switch in energy metabolism-glycolysis to fatty acid oxidation. The molecular factors regulating this metabolic switch remain largely unexplored. We first demonstrate that the molecular signatures in 1-year (y) matured human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are similar to those seen in in vivo-derived mature cardiac tissues, thus making them an excellent model to study human cardiac maturation. We further show that let-7 is the most highly up-regulated microRNA (miRNA) family during in vitro human cardiac maturation. Gain- and loss-of-function analyses of let-7g in hESC-CMs demonstrate it is both required and sufficient for maturation, but not for early differentiation of CMs. Overexpression of let-7 family members in hESC-CMs enhances cell size, sarcomere length, force of contraction, and respiratory capacity. Interestingly, large-scale expression data, target analysis, and metabolic flux assays suggest this let-7-driven CM maturation could be a result of down-regulation of the phosphoinositide 3 kinase (PI3K)/AKT protein kinase/insulin pathway and an up-regulation of fatty acid metabolism. These results indicate let-7 is an important mediator in augmenting metabolic energetics in maturing CMs. Promoting maturation of hESC-CMs with let-7 overexpression will be highly significant for basic and applied research.
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