ArticleProceedings of the National Academy of Sciences of the United States of America2013
Reprogramming of human fibroblasts toward a cardiac fate.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers, 3 of them syntheses 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
291 citing papers in PubMed, 3 syntheses or guidelines pooled it, 504 citations in OpenAlex.
- Advances in Stem Cell Therapy for Huntington's Disease: A Comprehensive Literature Review.Cells · 2025Pooled it
- Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis.International journal of molecular sciences · 2020Pooled it
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Integrating delivery systems and microenvironmental cues to accelerate clinical translation of cardiac reprogramming.Materials today. Bio · 2026Review
- Impact ofJournal of cardiovascular development and disease · 2026Review
- Spatial expression of myocardin protein in normal and disease states.American journal of physiology. Cell physiology · 2026Article
- The cardiac 4D nucleome: nuclear and chromatin dynamics across development, disease and ageing.Nature reviews. Cardiology · 2026Review
- Advances in MicroRNA-Based Therapies for Cardiac Repair: Emerging Strategies for Treating Myocardial Infarction.Molecular and cellular biochemistry · 2026Review
- Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026Review
- Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026Review
- Cell-free strategies for cardiomyocyte proliferation and heart repair.Pharmacological reports : PR · 2026Review
- Heart Regeneration for Clinical Application.Internal medicine (Tokyo, Japan) · 2026Review
- Administration of a novel reprogramming formula improves cardiac function and decreases cardiac fibrosis in a myocardial infarction model.JTCVS open · 2025Article
- Blocking nuclear receptor Nr4a3 unlocks the senescence barrier to promote direct cardiac reprogramming.Science advances · 2025Article
- Novel Directly Reprogrammed Smooth Muscle Cells Promote Vascular Regeneration as Microvascular Mural Cells.Circulation · 2025Article
- Cell Reprogramming, Transdifferentiation, and Dedifferentiation Approaches for Heart Repair.International journal of molecular sciences · 2025Review
- Review
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Proregenerative MicroRNAs to Repair the Damaged Heart.European cardiology · 2025Review
- Review
231 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Reprogramming of mouse fibroblasts toward a myocardial cell fate by forced expression of cardiac transcription factors or microRNAs has recently been demonstrated. The potential clinical applicability of these findings is based on the minimal regenerative potential of the adult human heart and the limited availability of human heart tissue. An initial but mandatory step toward clinical application of this approach is to establish conditions for conversion of adult human fibroblasts to a cardiac phenotype. Toward this goal, we sought to determine the optimal combination of factors necessary and sufficient for direct myocardial reprogramming of human fibroblasts. Here we show that four human cardiac transcription factors, including GATA binding protein 4, Hand2, T-box5, and myocardin, and two microRNAs, miR-1 and miR-133, activated cardiac marker expression in neonatal and adult human fibroblasts. After maintenance in culture for 4-11 wk, human fibroblasts reprogrammed with these proteins and microRNAs displayed sarcomere-like structures and calcium transients, and a small subset of such cells exhibited spontaneous contractility. These phenotypic changes were accompanied by expression of a broad range of cardiac genes and suppression of nonmyocyte genes. These findings indicate that human fibroblasts can be reprogrammed to cardiac-like myocytes by forced expression of cardiac transcription factors with muscle-specific microRNAs and represent a step toward possible therapeutic application of this reprogramming approach.
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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.