ArticleCirculation2022
Metabolic Changes Associated With Cardiomyocyte Dedifferentiation Enable Adult Mammalian Cardiac Regeneration.
Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- Human adult and pediatric multimodal transcriptomic atlas of progression from pressure-loaded to failing right ventricle.Nature cardiovascular research · 2026Article
- A Spatiotemporal Single-Cell Atlas Uncovers Dysregulated ECM Dynamics and Septal Remodeling Arrest in Human Ventricular Septal Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cardiac immunity and heart repair: Mechanism, challenge, and future direction.Chinese medical journal · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Bench to Bedside: Insights from Large Animal Models and Emerging Clinical Trials of Endogenous Cardiac Regeneration and Repair.Journal of cardiovascular translational research · 2026Review
- Deletion of activating transcription factor 3 (Atf3) promotes cardiomyocyte differentiation from embryonic stem cells.Scientific reports · 2026Article
- Long non-coding RNAs as modulators of metabolic reprogramming for endogenous heart regeneration: Mechanisms and therapeutic potential.Biomedical journal · 2026Review
- Rejuvenating the damaged and aged heart: lessons from development.npj biomedical innovations · 2026Review
- Modular bioreactor for multi-well electrical stimulation ofLab on a chip · 2026Article
- Sodium Alginate Attenuates HMolecular biotechnology · 2026Article
- Human Hearts Intrinsically Increase Cardiomyocyte Mitosis After Myocardial Infarction.Circulation research · 2026Article
- Predicting metabolic preferences through transcriptomics: a data-driven approach to align metabolic signatures with gene expression profiles.Biochemistry and biophysics reports · 2025Article
- CDC5L facilitates cardiomyocyte proliferation and ameliorates myocardial ischemia-reperfusion injury via modulation of the FGF10-YAP axis.Acta biochimica et biophysica Sinica · 2025Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Spatiotemporal dynamics of the cardioimmune niche during lesion repair.Nature cardiovascular research · 2025Article
- Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF).Cardiovascular research · 2025Article
- Review
- Rewiring cell identity and metabolism to drive cardiomyocyte proliferation.Cell regeneration (London, England) · 2025Review
- Transcriptional, proteomic and metabolic drivers of cardiac regeneration.Heart (British Cardiac Society) · 2025Review
- Knockout of thyroid hormone receptor alpha a (thraa) enhances cardiac regeneration in zebrafish through metabolic and hypoxic regulation.Cell communication and signaling : CCS · 2025Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundCardiac regeneration after injury is limited by the low proliferative capacity of adult mammalian cardiomyocytes (CMs). However, certain animals readily regenerate lost myocardium through a process involving dedifferentiation, which unlocks their proliferative capacities.
methodsWe bred mice with inducible, CM-specific expression of the Yamanaka factors, enabling adult CM reprogramming and dedifferentiation in vivo.
resultsTwo days after induction, adult CMs presented a dedifferentiated phenotype and increased proliferation in vivo. Microarray analysis revealed that upregulation of ketogenesis was central to this process. Adeno-associated virus-driven HMGCS2 overexpression induced ketogenesis in adult CMs and recapitulated CM dedifferentiation and proliferation observed during partial reprogramming. This same phenomenon was found to occur after myocardial infarction, specifically in the border zone tissue, and HMGCS2 knockout mice showed impaired cardiac function and response to injury. Finally, we showed that exogenous HMGCS2 rescues cardiac function after ischemic injury.
conclusionsOur data demonstrate the importance of HMGCS2-induced ketogenesis as a means to regulate metabolic response to CM injury, thus allowing cell dedifferentiation and proliferation as a regenerative response.
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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.