ArticleCirculation2024
MBNL1 Regulates Programmed Postnatal Switching Between Regenerative and Differentiated Cardiac States.
Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- RNA-Binding Protein Signature in Proliferative Cardiomyocytes: A Cross-Species Meta-Analysis from Mouse, Pig, and Human Transcriptomic Profiling Data.Biomolecules · 2025Pooled it
- Environmental cues signal through circadian control of sarcomeric gene expression during cardiomyocyte hypertrophy.Epigenetics · 2026Article
- Empagliflozin restores cardiac function in obese-diabetic HFpEF mice but further alters gene expression.Basic research in cardiology · 2026Article
- Bench to Bedside: Insights from Large Animal Models and Emerging Clinical Trials of Endogenous Cardiac Regeneration and Repair.Journal of cardiovascular translational research · 2026Review
- Doxorubicin exposure leads to cardiac fibroblast dysregulation and worsens fibrotic remodeling in the pathological heart.Journal of molecular and cellular cardiology plus · 2026Article
- Retinol saturase in the mitochondria antagonizes IDH2 and GLUD1 acetylation to mediate heart repair.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome profiles in two HFpEF murine models: etiology and sex-dependent differences.American journal of physiology. Heart and circulatory physiology · 2026Article
- Co-Opting MBNL-Dependent Alternative Splicing Cassette Exons to Control Gene Therapy in Myotonic Dystrophy.Annals of neurology · 2026Article
- Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy.Science (New York, N.Y.) · 2025Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Mbnl1 Protects Against Cerebral Ischemia-Reperfusion Injury by Modulating Microglia/Macrophage Polarization via NF-κB Pathway.Molecular neurobiology · 2025Article
- Rewiring cell identity and metabolism to drive cardiomyocyte proliferation.Cell regeneration (London, England) · 2025Review
- Decoding Cardiac Maturation Program: Insights from RNA Splicing Regulation.Current cardiology reports · 2025Review
- MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model.The Journal of clinical investigation · 2025Article
- MBNL splicing factors regulate the microtranscriptome of skeletal muscles.Nucleic acids research · 2024Article
- Seeing is Believing: Muscleblind-like 1 Is Necessary For Mammalian Cardiomyocyte Maturation.Circulation · 2024Article
- Targeting cardiomyocyte cell cycle regulation in heart failure.Basic research in cardiology · 2024Review
- Cardiac maturation.Journal of molecular and cellular cardiology · 2024Review
- RNA binding proteins as mediators of pathological cardiac remodeling.Frontiers in cell and developmental biology · 2024Review
- RNA-Binding Proteins as Critical Post-Transcriptional Regulators of Cardiac Regeneration.International journal of molecular sciences · 2023Review
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundDiscovering determinants of cardiomyocyte maturity is critical for deeply understanding the maintenance of differentiated states and potentially reawakening endogenous regenerative programs in adult mammalian hearts as a therapeutic strategy. Forced dedifferentiation paired with oncogene expression is sufficient to drive cardiac regeneration, but elucidation of endogenous developmental regulators of the switch between regenerative and mature cardiomyocyte cell states is necessary for optimal design of regenerative approaches for heart disease. MBNL1 (muscleblind-like 1) regulates fibroblast, thymocyte, and erythroid differentiation and proliferation. Hence, we examined whether MBNL1 promotes and maintains mature cardiomyocyte states while antagonizing cardiomyocyte proliferation.
methodsMBNL1 gain- and loss-of-function mouse models were studied at several developmental time points and in surgical models of heart regeneration. Multi-omics approaches were combined with biochemical, histological, and in vitro assays to determine the mechanisms through which MBNL1 exerts its effects.
resultsMBNL1 is coexpressed with a maturation-association genetic program in the heart and is regulated by the MEIS1/calcineurin signaling axis. Targeted MBNL1 overexpression early in development prematurely transitioned cardiomyocytes to hypertrophic growth, hypoplasia, and dysfunction, whereas loss of MBNL1 function increased cardiomyocyte cell cycle entry and proliferation through altered cell cycle inhibitor transcript stability. Moreover, MBNL1-dependent stabilization of estrogen-related receptor signaling was essential for maintaining cardiomyocyte maturity in adult myocytes. In accordance with these data, modulating MBNL1 dose tuned the temporal window of neonatal cardiac regeneration, where increased MBNL1 expression arrested myocyte proliferation and regeneration and MBNL1 deletion promoted regenerative states with prolonged myocyte proliferation. However, MBNL1 deficiency was insufficient to promote regeneration in the adult heart because of cell cycle checkpoint activation.
conclusionsHere, MBNL1 was identified as an essential regulator of cardiomyocyte differentiated states, their developmental switch from hyperplastic to hypertrophic growth, and their regenerative potential through controlling an entire maturation program by stabilizing adult myocyte mRNAs during postnatal development and throughout adulthood. Targeting loss of cardiomyocyte maturity and downregulation of cell cycle inhibitors through MBNL1 deletion was not sufficient to promote adult regeneration.
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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.