Cardiac Regeneration in Non-Mammalian Vertebrates

A special issue of Journal of Cardiovascular Development and Disease (ISSN 2308-3425).

Deadline for manuscript submissions: closed (31 October 2018) | Viewed by 30046

Special Issue Editor


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Guest Editor
Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, Australia
Interests: organ regeneration; cardiomyocyte proliferation; cardiomyocyte dedifferentiation; immune cell function; conditional knockout analysis

Special Issue Information

Dear Colleagues,

JCDD is launching a Special Issue on "Cardiac Regeneration in Non-Mammalian Vertebrates", which focuses on recent advances in understanding the genetic, molecular, and cellular mechanisms underpinning robust regeneration of a damaged heart in non-mammalian vertebrates, such as zebrafish and salamanders. Research using non-mammalian vertebrates has inspired new priorities in cardiac regeneration science. For example, classical and recent studies using newts and axolotls provided evidence for cell cycle re-entry of differentiated cardiomyocytes after injury. More recently, genetic fate-mapping studies using zebrafish definitively identified cardiomyocytes (not stem cells) as the primary cellular source for muscle replacement during regeneration, significantly influencing the direction of the field in seeking future therapies focused on cardiomyocyte renewal to repair human hearts. Knowledge is still limited, but the field has been rapidly evolving in the last decade with new genetic approaches including conditional gene expression techniques and targeted mutagenesis, providing insights that may help to understand how cardiac regeneration naturally proceeds in the permissive animals and the cellular and molecular roadblocks to mammalian adult organ regeneration. This Special Issue will provide a platform to discuss current understanding of the endogenous mechanisms of cardiac regeneration in non-mammalian vertebrates which brings hope of providing new directions for future investigation into this burgeoning and exciting area of regeneration science.

Dr. Kazu Kikuchi
Guest Editor

Manuscript Submission Information

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Keywords

  • Heart regeneration
  • Myocardial infarction
  • Heart failure
  • Dedifferentiation
  • Transdifferentiation
  • Reprogramming
  • Cardiomyocytes
  • Cardiomyocyte proliferation
  • Zebrafish
  • Axolotl
  • Newt
  • Animal models

Published Papers (6 papers)

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Review

12 pages, 688 KiB  
Review
Emerging Roles for Immune Cells and MicroRNAs in Modulating the Response to Cardiac Injury
by Adriana M. Rodriguez and Viravuth P. Yin
J. Cardiovasc. Dev. Dis. 2019, 6(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd6010005 - 15 Jan 2019
Cited by 6 | Viewed by 3376
Abstract
Stimulating cardiomyocyte regeneration after an acute injury remains the central goal in cardiovascular regenerative biology. While adult mammals respond to cardiac damage with deposition of rigid scar tissue, adult zebrafish and salamander unleash a regenerative program that culminates in new cardiomyocyte formation, resolution [...] Read more.
Stimulating cardiomyocyte regeneration after an acute injury remains the central goal in cardiovascular regenerative biology. While adult mammals respond to cardiac damage with deposition of rigid scar tissue, adult zebrafish and salamander unleash a regenerative program that culminates in new cardiomyocyte formation, resolution of scar tissue, and recovery of heart function. Recent studies have shown that immune cells are key to regulating pro-inflammatory and pro-regenerative signals that shift the injury microenvironment toward regeneration. Defining the genetic regulators that control the dynamic interplay between immune cells and injured cardiac tissue is crucial to decoding the endogenous mechanism of heart regeneration. In this review, we discuss our current understanding of the extent that macrophage and regulatory T cells influence cardiomyocyte proliferation and how microRNAs (miRNAs) regulate their activity in the injured heart. Full article
(This article belongs to the Special Issue Cardiac Regeneration in Non-Mammalian Vertebrates)
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12 pages, 1654 KiB  
Review
Covering and Re-Covering the Heart: Development and Regeneration of the Epicardium
by Yingxi Cao and Jingli Cao
J. Cardiovasc. Dev. Dis. 2019, 6(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd6010003 - 24 Dec 2018
Cited by 10 | Viewed by 5363
Abstract
The epicardium, a mesothelial layer that envelops vertebrate hearts, has become a therapeutic target in cardiac repair strategies because of its vital role in heart development and cardiac injury response. Epicardial cells serve as a progenitor cell source and signaling center during both [...] Read more.
The epicardium, a mesothelial layer that envelops vertebrate hearts, has become a therapeutic target in cardiac repair strategies because of its vital role in heart development and cardiac injury response. Epicardial cells serve as a progenitor cell source and signaling center during both heart development and regeneration. The importance of the epicardium in cardiac repair strategies has been reemphasized by recent progress regarding its requirement for heart regeneration in zebrafish, and by the ability of patches with epicardial factors to restore cardiac function following myocardial infarction in mammals. The live surveillance of epicardial development and regeneration using zebrafish has provided new insights into this topic. In this review, we provide updated knowledge about epicardial development and regeneration. Full article
(This article belongs to the Special Issue Cardiac Regeneration in Non-Mammalian Vertebrates)
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12 pages, 984 KiB  
Review
Transcriptional Programs and Regeneration Enhancers Underlying Heart Regeneration
by Ian J. Begeman and Junsu Kang
J. Cardiovasc. Dev. Dis. 2019, 6(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd6010002 - 22 Dec 2018
Cited by 6 | Viewed by 4875
Abstract
The heart plays the vital role of propelling blood to the entire body, which is essential to life. While maintaining heart function is critical, adult mammalian hearts poorly regenerate damaged cardiac tissue upon injury and form scar tissue instead. Unlike adult mammals, adult [...] Read more.
The heart plays the vital role of propelling blood to the entire body, which is essential to life. While maintaining heart function is critical, adult mammalian hearts poorly regenerate damaged cardiac tissue upon injury and form scar tissue instead. Unlike adult mammals, adult zebrafish can regenerate injured hearts with no sign of scarring, making zebrafish an ideal model system with which to study the molecular mechanisms underlying heart regeneration. Investigation of heart regeneration in zebrafish together with mice has revealed multiple cardiac regeneration genes that are induced by injury to facilitate heart regeneration. Altered expression of these regeneration genes in adult mammals is one of the main causes of heart regeneration failure. Previous studies have focused on the roles of these regeneration genes, yet the regulatory mechanisms by which the expression of cardiac regeneration genes is precisely controlled are largely unknown. In this review, we will discuss the importance of differential gene expression for heart regeneration, the recent discovery of cardiac injury or regeneration enhancers, and their impact on heart regeneration. Full article
(This article belongs to the Special Issue Cardiac Regeneration in Non-Mammalian Vertebrates)
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17 pages, 1642 KiB  
Review
Coronary Vasculature in Cardiac Development and Regeneration
by Subir Kapuria, Tyler Yoshida and Ching-Ling Lien
J. Cardiovasc. Dev. Dis. 2018, 5(4), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd5040059 - 17 Dec 2018
Cited by 17 | Viewed by 5268
Abstract
Functional coronary circulation is essential for a healthy heart in warm-blooded vertebrates, and coronary diseases can have a fatal consequence. Despite the growing interest, the knowledge about the coronary vessel development and the roles of new coronary vessel formation during heart regeneration is [...] Read more.
Functional coronary circulation is essential for a healthy heart in warm-blooded vertebrates, and coronary diseases can have a fatal consequence. Despite the growing interest, the knowledge about the coronary vessel development and the roles of new coronary vessel formation during heart regeneration is still limited. It is demonstrated that early revascularization is required for efficient heart regeneration. In this comprehensive review, we first describe the coronary vessel formation from an evolutionary perspective. We further discuss the cell origins of coronary endothelial cells and perivascular cells and summarize the critical signaling pathways regulating coronary vessel development. Lastly, we focus on the current knowledge about the molecular mechanisms regulating heart regeneration in zebrafish, a genetically tractable vertebrate model with a regenerative adult heart and well-developed coronary system. Full article
(This article belongs to the Special Issue Cardiac Regeneration in Non-Mammalian Vertebrates)
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14 pages, 1170 KiB  
Review
Epigenetic Regulation of Organ Regeneration in Zebrafish
by Xiaojun Zhu, Chenglu Xiao and Jing-Wei Xiong
J. Cardiovasc. Dev. Dis. 2018, 5(4), 57; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd5040057 - 14 Dec 2018
Cited by 11 | Viewed by 5162
Abstract
The zebrafish is broadly used for investigating de novo organ regeneration, because of its strong regenerative potential. Over the past two decades of intense study, significant advances have been made in identifying both the regenerative cell sources and molecular signaling pathways in a [...] Read more.
The zebrafish is broadly used for investigating de novo organ regeneration, because of its strong regenerative potential. Over the past two decades of intense study, significant advances have been made in identifying both the regenerative cell sources and molecular signaling pathways in a variety of organs in adult zebrafish. Epigenetic regulation has gradually moved into the center-stage of this research area, aided by comprehensive work demonstrating that DNA methylation, histone modifications, chromatin remodeling complexes, and microRNAs are essential for organ regeneration. Here, we present a brief review of how these epigenetic components are induced upon injury, and how they are involved in sophisticated organ regeneration. In addition, we highlight several prospective research directions and their potential implications for regenerative medicine. Full article
(This article belongs to the Special Issue Cardiac Regeneration in Non-Mammalian Vertebrates)
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10 pages, 588 KiB  
Review
Endothelial Contributions to Zebrafish Heart Regeneration
by Cristina E. Fernandez, Melanie Bakovic and Ravi Karra
J. Cardiovasc. Dev. Dis. 2018, 5(4), 56; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd5040056 - 11 Dec 2018
Cited by 14 | Viewed by 5562
Abstract
Studies over the past two decades have shown heart regeneration in zebrafish to be a dynamic process, choreographed by multiple cell types. In particular, recent work has identified revascularization of the wound to be a sentinel event during heart regeneration. The cardiac endothelium [...] Read more.
Studies over the past two decades have shown heart regeneration in zebrafish to be a dynamic process, choreographed by multiple cell types. In particular, recent work has identified revascularization of the wound to be a sentinel event during heart regeneration. The cardiac endothelium has emerged as a key orchestrator of heart regeneration, influencing cardiomyocyte hyperplasia and tissue morphogenesis. Here, we review how the coronary vasculature regenerates after injury, how signaling pathways link the cardiac endothelium to heart regeneration, and how understanding these signaling dynamics can lead to targeted therapies for heart regeneration. Full article
(This article belongs to the Special Issue Cardiac Regeneration in Non-Mammalian Vertebrates)
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