ArticleProtein & cell2023
Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.
Article in Protein & cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Leukemic Transdifferentiation: From Pathological Plasticity to Dendritic Cell-Based Immunotherapy.Biomedicines · 2025Review
- Kdm7aa Orchestrates an Immunomodulatory Cardiomyocyte Program to Enable Zebrafish Heart Regeneration.International journal of molecular sciences · 2025Article
- Advances in Epicardial Biology: Insights from Development, Regeneration, and Human Cardiac Organoids.Journal of cardiovascular development and disease · 2025Review
- Flavonifractor Plautii or Its Metabolite Desaminotyrosine as Prophylactic Agents for Alleviating Myocardial Ischemia/Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ROS-Mediated Unfolded Protein Response Activation Drives Hepatocyte Apoptosis in Mesaconitine-Induced Liver Injury.Toxics · 2025Article
- The Application of Epicardium in Heart Failure Treatment: Opportunities and Challenges.International journal of medical sciences · 2025Review
- Ochratoxin A induces immunotoxicity by targeting Annexin A1 mediated neutrophil apoptosis in zebrafish.Frontiers in immunology · 2025Article
- Heart regeneration from the whole-organism perspective to single-cell resolution.NPJ Regenerative medicine · 2024Review
- Angiopoietin-4 expression and potential mechanisms in carcinogenesis: Current achievements and perspectives.Clinical and experimental medicine · 2024Review
- Angiopoietin4 (ANGPT4) expression and potential mechanisms in carcinogenesis: current achievements and perspectives.Clinical and experimental medicine · 2023Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
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Registered trials
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