ArticleProceedings of the National Academy of Sciences of the United States of America2015
Akt1/protein kinase B enhances transcriptional reprogramming of fibroblasts to functional cardiomyocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 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
112 citing papers in PubMed, 1 synthesis or guideline pooled 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
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Cellular Reprogramming by PHF7 Enhances Cardiac Function Following Myocardial Infarction.Circulation · 2025Article
- 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
- Cell Reprogramming, Transdifferentiation, and Dedifferentiation Approaches for Heart Repair.International journal of molecular sciences · 2025Review
- Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025Review
- Decoding the epigenetic and transcriptional basis of direct cardiac reprogramming.Stem cells (Dayton, Ohio) · 2025Review
- Review
- Review
- Macrophages suppress cardiac reprogramming of fibroblasts in vivo via IFN-mediated intercellular self-stimulating circuit.Protein & cell · 2024Article
- Control of cell fate upon transcription factor-driven cardiac reprogramming.Current opinion in genetics & development · 2024Review
- Modifying miRs for effective reprogramming of fibroblasts to cardiomyocytes.Molecular therapy. Nucleic acids · 2024Article
- 14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.Cell reports · 2024Article
- Regenerative loss in the animal kingdom as viewed from the mouse digit tip and heart.Developmental biology · 2024Review
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- Fibroblast Reprogramming in Cardiac Repair.JACC. Basic to translational science · 2024Review
- Robust small molecule-aided cardiac reprogramming systems selective to cardiac fibroblasts.iScience · 2023Article
- A novel transcription factor combination for direct reprogramming to a spontaneously contracting human cardiomyocyte-like state.Journal of molecular and cellular cardiology · 2023Article
- Prospective of Pancreatic Cancer Diagnosis Using Cardiac Sensing.Journal of imaging · 2023Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
Conversion of fibroblasts to functional cardiomyocytes represents a potential approach for restoring cardiac function after myocardial injury, but the technique thus far has been slow and inefficient. To improve the efficiency of reprogramming fibroblasts to cardiac-like myocytes (iCMs) by cardiac transcription factors [Gata4, Hand2, Mef2c, and Tbx5 (GHMT)], we screened 192 protein kinases and discovered that Akt/protein kinase B dramatically accelerates and amplifies this process in three different types of fibroblasts (mouse embryo, adult cardiac, and tail tip). Approximately 50% of reprogrammed mouse embryo fibroblasts displayed spontaneous beating after 3 wk of induction by Akt plus GHMT. Furthermore, addition of Akt1 to GHMT evoked a more mature cardiac phenotype for iCMs, as seen by enhanced polynucleation, cellular hypertrophy, gene expression, and metabolic reprogramming. Insulin-like growth factor 1 (IGF1) and phosphoinositol 3-kinase (PI3K) acted upstream of Akt whereas the mitochondrial target of rapamycin complex 1 (mTORC1) and forkhead box o3 (Foxo3a) acted downstream of Akt to influence fibroblast-to-cardiomyocyte reprogramming. These findings provide insights into the molecular basis of cardiac reprogramming and represent an important step toward further application of this technique.
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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.