ArticleCirculation2020
Inhibition of mTOR Signaling Enhances Maturation of Cardiomyocytes Derived From Human-Induced Pluripotent Stem Cells via p53-Induced Quiescence.
Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation.Frontiers in cardiovascular medicine · 2022Pooled it
- Maternal Exercise and Offspring Cardiac Regenerative Potential: Roles of Apelin and α-Ketoglutarate.Biology · 2026Review
- PRDM16 modulates aspects of cell cycle dynamics and maturation in human iPSC-derived cardiomyocytes.Stem cell reports · 2026Article
- Impact of maternal lipopolysaccharide and polyinosinic-polycytidylic acid-induced infections on offspring cardiac development: Mitochondrial dysfunction and metabolic alterations.Genes & diseases · 2026Article
- RRAGD p.(Ser76Leu) Variant Causes Dysregulated Expression of Muscle Development and Cytoskeleton Genes in Cardiomyocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Metabolic changes during cardiac regeneration in the axolotl.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- TCA cycle intermediates as an adjunct strategy for human iPSC-derived cardiomyocyte maturation.BBA advances · 2026Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- AIBP-LRP2-mediated HDL uptake restricts CXCR4Science advances · 2025Article
- Au@Pt Nanoparticles Enhance Maturation and Contraction of Mouse Embryonic Stem Cells-Derived and Neonatal Mouse Cardiomyocytes.Tissue engineering and regenerative medicine · 2025Article
- Generation of mature epicardium derived from human-induced pluripotent stem cells via inhibition of mTOR signaling.Nature communications · 2025Article
- FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction.Nature communications · 2025Article
- The mTOR Signaling Pathway: Key Regulator and Therapeutic Target for Heart Disease.Biomedicines · 2025Review
- Induced pluripotent stem cell-derived cardiomyocyte in vitro models: benchmarking progress and ongoing challenges.Nature methods · 2025Review
- Cell cycle arrest of cardiomyocytes in the context of cardiac regeneration.Frontiers in cardiovascular medicine · 2025Review
- Transition from fetal to postnatal state in the heart: Crosstalk between metabolism and regeneration.Development, growth & differentiation · 2024Review
- The role and mechanism of NRG1/ErbB4 in inducing the differentiation of induced pluripotent stem cells into cardiomyocytes.BMC cardiovascular disorders · 2024Article
- SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3β/β-catenin&ERK signaling.Stem cell research & therapy · 2024Article
- Maturation of pluripotent stem cell-derived cardiomyocytes: limitations and challenges from metabolic aspects.Stem cell research & therapy · 2024Review
- P53 Activation Promotes Maturational Characteristics of Pluripotent Stem Cell-Derived Cardiomyocytes in 3-Dimensional Suspension Culture Via FOXO-FOXM1 Regulation.Journal of the American Heart Association · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundCurrent differentiation protocols to produce cardiomyocytes from human induced pluripotent stem cells (iPSCs) are capable of generating highly pure cardiomyocyte populations as determined by expression of cardiac troponin T. However, these cardiomyocytes remain immature, more closely resembling the fetal state, with a lower maximum contractile force, slower upstroke velocity, and immature mitochondrial function compared with adult cardiomyocytes. Immaturity of iPSC-derived cardiomyocytes may be a significant barrier to clinical translation of cardiomyocyte cell therapies for heart disease. During development, cardiomyocytes undergo a shift from a proliferative state in the fetus to a more mature but quiescent state after birth. The mechanistic target of rapamycin (mTOR)-signaling pathway plays a key role in nutrient sensing and growth. We hypothesized that transient inhibition of the mTOR-signaling pathway could lead cardiomyocytes to a quiescent state and enhance cardiomyocyte maturation.
methodsCardiomyocytes were differentiated from 3 human iPSC lines using small molecules to modulate the Wnt pathway. Torin1 (0 to 200 nmol/L) was used to inhibit the mTOR pathway at various time points. We quantified contractile, metabolic, and electrophysiological properties of matured iPSC-derived cardiomyocytes. We utilized the small molecule inhibitor, pifithrin-α, to inhibit p53 signaling, and nutlin-3a, a small molecule inhibitor of MDM2 (mouse double minute 2 homolog) to upregulate and increase activation of p53.
resultsTorin1 (200 nmol/L) increased the percentage of quiescent cells (G
conclusionsTransient treatment of human iPSC-derived cardiomyocytes with Torin1 shifts cells to a quiescent state and enhances cardiomyocyte maturity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.