ArticlePloS one2011
Distinct roles of microRNA-1 and -499 in ventricular specification and functional maturation of human embryonic stem cell-derived cardiomyocytes.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed.
- Impact of secretome containing extracellular vesicles from human induced pluripotent stem cell-derived cardiomyocytes.Regenerative therapy · 2026Article
- Advances in MicroRNA-Based Therapies for Cardiac Repair: Emerging Strategies for Treating Myocardial Infarction.Molecular and cellular biochemistry · 2026Review
- Recent Advances of Pluripotent Stem Cell-Derived Cardiomyocytes for Regenerative Medicine.Metabolites · 2025Review
- hiPSC-derived cardiac fibroblasts dynamically enhance the mechanical function of hiPSC-derived cardiomyocytes on an engineered substrate.Frontiers in bioengineering and biotechnology · 2025Article
- Maturation of pluripotent stem cell-derived cardiomyocytes: limitations and challenges from metabolic aspects.Stem cell research & therapy · 2024Review
- Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation.Clinical epigenetics · 2024Article
- miRNAs in Heart Development and Disease.International journal of molecular sciences · 2024Review
- MicroRNA-1 Deficiency Is a Primary Etiological Factor Disrupting Cardiac Contractility and Electrophysiological Homeostasis.Circulation. Arrhythmia and electrophysiology · 2024Article
- Review
- Integrated modeling framework reveals co-regulation of transcription factors, miRNAs and lncRNAs on cardiac developmental dynamics.Stem cell research & therapy · 2023Article
- Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2023Review
- The Essential Function of miR-5739 in Embryonic Muscle Development.International journal of stem cells · 2023Article
- New Insight into Mechanisms of Cardiovascular Diseases: An Integrative Analysis Approach to Identify TheranoMiRNAs.International journal of molecular sciences · 2023Article
- Cardiac microRNAs: diagnostic and therapeutic potential.Archives of medical science : AMS · 2023Article
- Non-coding RNAs: key regulators of reprogramming, pluripotency, and cardiac cell specification with therapeutic perspective for heart regeneration.Cardiovascular research · 2022Review
- The negative regulation of gene expression by microRNAs as key driver of inducers and repressors of cardiomyocyte differentiation.Clinical science (London, England : 1979) · 2022Review
- Tissue Engineering Techniques for Induced Pluripotent Stem Cell Derived Three-Dimensional Cardiac Constructs.Tissue engineering. Part B, Reviews · 2022Review
- Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell-Cardiomyocyte Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Multilayer control of cardiac electrophysiology by microRNAs.Journal of molecular and cellular cardiology · 2022Review
- Maturation of Stem Cell-Derived Cardiomyocytes: Foe in Translation Medicine.International journal of stem cells · 2021Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
Abstract
backgroundMicroRNAs (miRs) negatively regulate transcription and are important determinants of normal heart development and heart failure pathogenesis. Despite the significant knowledge gained in mouse studies, their functional roles in human (h) heart remain elusive. METHODS AND
resultsWe hypothesized that miRs that figure prominently in cardiac differentiation are differentially expressed in differentiating, developing, and terminally mature human cardiomyocytes (CMs). As a first step, we mapped the miR profiles of human (h) embryonic stem cells (ESCs), hESC-derived (hE), fetal (hF) and adult (hA) ventricular (V) CMs. 63 miRs were differentially expressed between hESCs and hE-VCMs. Of these, 29, including the miR-302 and -371/372/373 clusters, were associated with pluripotency and uniquely expressed in hESCs. Of the remaining miRs differentially expressed in hE-VCMs, 23 continued to express highly in hF- and hA-VCMs, with miR-1, -133, and -499 displaying the largest fold differences; others such as miR-let-7a, -let-7b, -26b, -125a and -143 were non-cardiac specific. Functionally, LV-miR-499 transduction of hESC-derived cardiovascular progenitors significantly increased the yield of hE-VCMs (to 72% from 48% of control; p<0.05) and contractile protein expression without affecting their electrophysiological properties (p>0.05). By contrast, LV-miR-1 transduction did not bias the yield (p>0.05) but decreased APD and hyperpolarized RMP/MDP in hE-VCMs due to increased I(to), I(Ks) and I(Kr), and decreased I(f) (p<0.05) as signs of functional maturation. Also, LV-miR-1 but not -499 augmented the immature Ca(2+) transient amplitude and kinetics. Molecular pathway analyses were performed for further insights.
conclusionWe conclude that miR-1 and -499 play differential roles in cardiac differentiation of hESCs in a context-dependent fashion. While miR-499 promotes ventricular specification of hESCs, miR-1 serves to facilitate electrophysiological maturation.
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