ArticleScience (New York, N.Y.)2015
HEART DISEASE. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05180188 (A Clinical Trial, Investigating the Effect of a Home-based Moderate Intensity Training Program on Oxidative Capacity and Hemodynamics in Patients With Truncating Genetic Variants in TTN.), which is not on this map. Cited by 374 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.
The trial behind it
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.
A Clinical Trial, Investigating the Effect of a Home-based Moderate Intensity Training Program on Oxidative Capacity and Hemodynamics in Patients With Truncating Genetic Variants in TTN.
Who cites it
374 citing papers in PubMed, 1 synthesis or guideline pooled it, 636 citations in OpenAlex.
- Geographical and Ethnic Heterogeneity in Genetic Dilated Cardiomyopathies.International journal of molecular sciences · 2026Pooled it
- Contribution of Noncanonical Splice Variants toCirculation. Genomic and precision medicine · 2021Trial
- Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency.Circulation research · 2021Trial
- Nx3 Is a Z-Disk Structural and Signaling Hub That Is Reduced in Heart Failure.Circulation research · 2026Article
- Genetic vulnerability and dynamic mechanical stress synergistically drive sarcomere failure in human iPSC-derived cardiomyocytes.Materials today. Bio · 2026Article
- SGLT2 inhibition improves sarcomere contractile dysfunction in human models of dilated cardiomyopathy.Journal of translational medicine · 2026Article
- Flexible Sensing Technology for Myocardial Tissue Contractile Force With Integrated Magnetically Actuated Mechanical Stimulation.Advanced healthcare materials · 2026Article
- A titin truncating variant linked to atrial fibrillation increases atrial profibrotic signalling and cholinergic sensitivity.Cardiovascular research · 2026Article
- Targeting intracellular cholesterol imbalance rescues sarcomere-ER contact site signaling and ER remodeling in dilated cardiomyopathy.Signal transduction and targeted therapy · 2026Article
- Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis.Nature cardiovascular research · 2026Article
- Review
- Advanced in vitro cardiac models for drug evaluation: integration of organoids, engineered tissues, and microphysiological systems.Microsystems & nanoengineering · 2026Review
- Review
- Unveiling cellular mechanisms underlying MYZAP related dilated cardiomyopathy using patient specific hiPSC cardiomyocytes.Scientific reports · 2026Article
- Models of the human heart for biomedical research: Opportunities and challenges.Physiological reports · 2026Review
- Vascularized Cardiac Tissue Engineering: From Advances in Biofabrication to Translational Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Investigating PKD2 deficiency-associated cardiomyopathies using hESC-cardiomyocytes and bioengineered 3D ventricular cardiac tissue strips.Cell death & disease · 2026Article
- Cell shape and maturation impacts α-actinin-2 tension in iPSC-derived cardiomyocytes.APL bioengineering · 2026Article
- Pediatric dilated cardiomyopathy caused by TNNT2-R151W mutation: Modeling and rescue in patient-derived induced pluripotent stem cells and engineered heart tissue.Bioengineering & translational medicine · 2026Article
- Identification of disease-associated gene expression signatures for mechanistic insights and drug prediction in dilated cardiomyopathy-induced heart failure.Molecular and cellular biochemistry · 2026Article
314 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell-derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling.
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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.