ArticlePloS one2019
Induced cardiomyocyte maturation: Cardiac transcription factors are necessary but not sufficient.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Hemoglobin inhibits fibroblast-to-cardiomyocyte reprogramming via TLR2/TLR4-dependent chromatin compaction.Molecular therapy. Nucleic acids · 2026Article
- Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- RNA Therapies in Cardio-Kidney-Metabolic Syndrome: Advancing Disease Management.Journal of cardiovascular translational research · 2025Review
- Leveraging cardiac reprogramming with CRISPRa-SAM technology.Molecular therapy. Nucleic acids · 2025Article
- Direct Cardiac Reprogramming in the Age of Computational Biology.Journal of cardiovascular development and disease · 2024Review
- C166 EVs potentiate miR cardiac reprogramming via miR-148a-3p.Journal of molecular and cellular cardiology · 2024Article
- Can we stop one heart from breaking: triumphs and challenges in cardiac reprogramming.Current opinion in genetics & development · 2023Review
- Direct cardiac reprogramming: A new technology for cardiac repair.Journal of molecular and cellular cardiology · 2023Review
- Genome Editing and Cardiac Regeneration.Advances in experimental medicine and biology · 2023Article
- Direct Cardiac Epigenetic Reprogramming through Codelivery of 5'Azacytidine and miR-133a Nanoformulation.International journal of molecular sciences · 2022Article
- The use of new CRISPR tools in cardiovascular research and medicine.Nature reviews. Cardiology · 2022Review
- Basic and Translational Research in Cardiac Repair and Regeneration: JACC State-of-the-Art Review.Journal of the American College of Cardiology · 2021Review
- Control of cardiomyocyte differentiation timing by intercellular signaling pathways.Seminars in cell & developmental biology · 2021Review
- Enhancing cardiac reprogramming via synthetic RNA oligonucleotides.Molecular therapy. Nucleic acids · 2021Article
- Tailoring Cardiac Synthetic Transcriptional Modulation Towards Precision Medicine.Frontiers in cardiovascular medicine · 2021Review
- Acute and Chronic Cardiovascular Manifestations of COVID-19: Role for Endotheliopathy.Methodist DeBakey cardiovascular journal · 2021Review
- Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes That Govern Cardiomyocyte Maturation.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- MicroRNA-Mediated Direct Reprogramming of Human Adult Fibroblasts Toward Cardiac Phenotype.Frontiers in bioengineering and biotechnology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The process by which fibroblasts are directly reprogrammed into cardiomyocytes involves two stages; initiation and maturation. Initiation represents the initial expression of factors that induce fibroblasts to transdifferentiate into cardiomyocytes. Following initiation, the cell undergoes a period of maturation before becoming a mature cardiomyocyte. We wanted to understand the role of cardiac development transcription factors in the maturation process. We directly reprogram fibroblasts into cardiomyocytes by a combination of miRNAs (miR combo). The ability of miR combo to induce cardiomyocyte-specific genes in fibroblasts was lost following the knockdown of the cardiac transcription factors Gata4, Mef2C, Tbx5 and Hand2 (GMTH). To further clarify the role of GMTH in miR combo reprogramming we utilized a modified CRISPR-Cas9 approach to activate endogenous GMTH genes. Importantly, both miR combo and the modified CRISPR-Cas9 approach induced comparable levels of GMTH expression. While miR combo was able to reprogram fibroblasts into cardiomyocyte-like cells, the modified CRISPR-Cas9 approach could not. Indeed, we found that cardiomyocyte maturation only occurred with very high levels of GMT expression. Taken together, our data indicates that while endogenous cardiac transcription factors are insufficient to reprogram fibroblasts into mature cardiomyocytes, endogenous cardiac transcription factors are necessary for expression of maturation genes.
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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.