scholarly journals In Vivo Activation of a Conserved MicroRNA Program Induces Mammalian Heart Regeneration

2014 ◽  
Vol 15 (5) ◽  
pp. 589-604 ◽  
Author(s):  
Aitor Aguirre ◽  
Nuria Montserrat ◽  
Serena Zacchigna ◽  
Emmanuel Nivet ◽  
Tomoaki Hishida ◽  
...  
Keyword(s):  
Heart Regeneration ◽  
Mammalian Heart

scholarly journals In Vivo Activation of a Conserved MicroRNA Program Induces Mammalian Heart Regeneration

2014 ◽  
Vol 15 (6) ◽  
pp. 805
Author(s):  
Aitor Aguirre ◽  
Nuria Montserrat ◽  
Serena Zacchigna ◽  
Emmanuel Nivet ◽  
Tomoaki Hishida ◽  
...  
Keyword(s):  
Heart Regeneration ◽  
Mammalian Heart

scholarly journals Distinct epicardial gene regulatory programmes drive development and regeneration of the zebrafish heart

2021 ◽  
Author(s):  
Michael Weinberger ◽  
Filipa C. Simoes ◽  
Tatjana Sauka-Spengler ◽  
Paul R. Riley
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Heart Regeneration ◽  
Mammalian Heart ◽  
Gene Regulatory ◽  
Zebrafish Heart

Unlike the adult mammalian heart, which has limited regenerative capacity, the zebrafish heart can fully regenerate following injury. Reactivation of cardiac developmental programmes is considered key to successfully regenerating the heart, yet the regulatory elements underlying the response triggered upon injury and during development remain elusive. Organ-wide activation of the epicardium is essential for zebrafish heart regeneration and is considered a potential regenerative source to target in the mammalian heart. Here we compared the transcriptome and epigenome of the developing and regenerating zebrafish epicardium by integrating gene expression profiles with open chromatin ATAC-seq data. By generating gene regulatory networks associated with epicardial development and regeneration, we inferred genetic programmes driving each of these processes, which were largely distinct. We identified wt1a, wt1b, and the AP-1 subunits junbb, fosab and fosb as central regulators of the developing network, whereas hif1ab, zbtb7a, tbx2b and nrf1 featured as putative central regulators of the regenerating epicardial network. By interrogating developmental gene regulatory networks that drive cell-specific transcriptional heterogeneity, we tested novel subpopulation-related epicardial enhancers in vivo. Taken together, our work revealed striking differences between the regulatory blueprint deployed during epicardial development and regeneration. These findings challenge the dogma that heart regeneration is essentially a reactivation of developmental programmes, and provide important insights into epicardial regulation that can assist in developing therapeutic approaches to enable tissue regeneration in the adult mammalian heart.

scholarly journals Extending the time window of mammalian heart regeneration by thymosin beta 4

2014 ◽  
Vol 18 (12) ◽  
pp. 2417-2424 ◽  
Author(s):  
Liu Rui ◽  
Nie Yu ◽  
Lian Hong ◽  
He Feng ◽  
Han Chunyong ◽  
...  
Keyword(s):  
Time Window ◽  
Heart Regeneration ◽  
Thymosin Beta 4 ◽  
Mammalian Heart

Abstract 20134: Transcriptional Profiling Identifies Candidate Regulators of Neonatal Heart Regeneration

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Caitlin O’Meara ◽  
Joseph Wamstad ◽  
Laurie Boyer ◽  
Richard T Lee
Keyword(s):  
Cell Cycle ◽  
Transcriptional Profiling ◽  
Cardiac Regeneration ◽  
Heart Regeneration ◽  
Transcriptional Signature ◽  
Adult Mice ◽  
Neonatal Heart ◽  
Sirna Knockdown

Some higher organisms, such as zebrafish and neonatal mice, are capable of complete and sufficient regeneration of the myocardium following injury, which is thought to occur primarily by proliferation of pre-existing cardiomyocytes. Although adult humans and adult mice lack this cardiac regeneration potential, there is great interest in understanding how regeneration can occur in the heart so that we can activate this process in humans suffering from heart failure. The aim of our study was to identify mechanisms by which mature, post-mitotic adult cardiomyocytes can re-enter the cell cycle to ultimately facilitate heart regeneration following injury. We derived a core transcriptional signature of injury-induced cardiomyocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiomyocyte differentiation and in an in vitro cardiomyocyte explant model, as well as a neonatal heart resection model. We identified a panel of transcription factors, growth factors, and cytokines, whose expression significantly correlated with the differentiated state of the cell in all datasets examined, suggesting that these factors play a role in regulating cardiomyocyte cell state. Furthermore, potential upstream regulators of core differentially expressed networks were identified using Ingenuity Pathway Analysis and we found that one predicted regulator, interleukin-13 (IL13), significantly induced cardiomyocyte cell cycle activity and STAT6/STAT3 signaling in vitro. siRNA knockdown experiments demonstrated that STAT3/periostin and STAT6 signaling are critical for cardiomyocyte cell cycle activity in response to IL13. These data reveal novel insights into the transcriptional regulation of mammalian heart regeneration and provide the founding circuitry for identifying potential regulators for stimulating cardiomyocyte cell cycle activity.

scholarly journals In vivo cardiac reprogramming contributes to zebrafish heart regeneration

Nature ◽  
2013 ◽  
Vol 498 (7455) ◽  
pp. 497-501 ◽  
Author(s):  
Ruilin Zhang ◽  
Peidong Han ◽  
Hongbo Yang ◽  
Kunfu Ouyang ◽  
Derek Lee ◽  
...  
Keyword(s):  
Heart Regeneration ◽  
Zebrafish Heart

scholarly journals Multicellular Transcriptional Analysis of Mammalian Heart Regeneration

Circulation ◽  
2017 ◽  
Vol 136 (12) ◽  
pp. 1123-1139 ◽  
Author(s):  
Gregory A. Quaife-Ryan ◽  
Choon Boon Sim ◽  
Mark Ziemann ◽  
Antony Kaspi ◽  
Haloom Rafehi ◽  
...  
Keyword(s):  
Transcriptional Analysis ◽  
Heart Regeneration ◽  
Mammalian Heart

scholarly journals Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration

2016 ◽  
Vol 2 (11) ◽  
pp. e1600844 ◽  
Author(s):  
William C. W. Chen ◽  
Zhouguang Wang ◽  
Maria Azzurra Missinato ◽  
Dae Woo Park ◽  
Daniel Ward Long ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Adult Mouse ◽  
Contractile Function ◽  
Left Ventricular ◽  
Precursor Cell ◽  
Cell Populations ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Regenerative Capacity ◽  
Mammalian Heart

Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts. Given the high regenerative capacity of adult zebrafish hearts, we hypothesize that decellularized zebrafish cardiac ECM (zECM) made from normal or healing hearts can induce mammalian heart regeneration. Using zebrafish and mice as representative species of lower vertebrates and mammals, we show that a single administration of zECM, particularly the healing variety, enables cardiac functional recovery and regeneration of adult mouse heart tissues after acute myocardial infarction. zECM-treated groups exhibit proliferation of the remaining cardiomyocytes and multiple cardiac precursor cell populations and reactivation of ErbB2 expression in cardiomyocytes. Furthermore, zECM exhibits pro-proliferative and chemotactic effects on human cardiac precursor cell populations in vitro. These contribute to the structural preservation and correlate with significantly higher cardiac contractile function, notably less left ventricular dilatation, and substantially more elastic myocardium in zECM-treated hearts than control animals treated with saline or decellularized adult mouse cardiac ECM. Inhibition of ErbB2 activity abrogates beneficial effects of zECM administration, indicating the possible involvement of ErbB2 signaling in zECM-mediated regeneration. This study departs from conventional focuses on mammalian ECM and introduces a new approach for cardiac tissue regeneration.

scholarly journals In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

2021 ◽  
Author(s):  
Mira I. Pronobis ◽  
Susan Zheng ◽  
Sumeet P. Singh ◽  
Kenneth D. Poss
Keyword(s):  
Cell Types ◽  
Myocardial Cell ◽  
Protein Networks ◽  
Transgenic Zebrafish ◽  
Heart Regeneration ◽  
Interacting Protein ◽  
Membrane Compartment ◽  
Rho A ◽  
Erbb2 Signaling

AbstractStrategies have not been available until recently to uncover interacting protein networks specific to key cell types, their subcellular compartments, and their major regulators during complex in vivo events. Here we apply BioID2 proximity labeling to capture protein networks acting within cardiomyocytes during a key model of innate heart regeneration in zebrafish. Transgenic zebrafish expressing a promiscuous BirA2 localized to the entire myocardial cell or membrane compartment were generated, each identifying unique proteomes in adult cardiomyocytes that became altered during regeneration. BioID2 profiling for interactors with ErbB2, a co-receptor for the cardiomyocyte mitogen Nrg1, implicated Rho A as a target of ErbB2 signaling in cardiomyocytes. Blockade of Rho A during heart regeneration, or during cardiogenic stimulation by the mitogenic influences Nrg1, Vegfaa or Vitamin D, disrupted muscle creation. Our findings reveal proximity labeling as a useful resource to interrogate cell proteomes and signaling networks during tissue regeneration in zebrafish.

scholarly journals Chamber Specification During Direct Cardiac Reprogramming

2021 ◽  
Author(s):  
Zhentao Zhang ◽  
Jesse Villalpando ◽  
Wenhui Zhang ◽  
Young-Jae Nam
Keyword(s):  
Myocardial Infarction ◽  
Transcription Factors ◽  
Post Myocardial Infarction ◽  
Heart Regeneration ◽  
Proof Of Concept ◽  
Major Fraction ◽  
Regenerative Approach ◽  
Inherent Advantage

Abstract Forced expression of core cardiogenic transcription factors can directly reprogram fibroblasts to induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. This cardiac reprogramming approach provides a proof of concept for induced heart regeneration by converting a fibroblast fate to a cardiomyocyte fate. However, it remains elusive whether chamber-specific cardiomyocytes can be generated by cardiac reprogramming. Therefore, we assessed the ability of the cardiac reprogramming approach for chamber specification in vitro and in vivo. We found that in vivo cardiac reprogramming post-myocardial infarction exclusively generates ventricular-like iCMs, while a major fraction of iCMs generated in vitro fail to determine their chamber identities. Our results indicate that in vivo cardiac reprogramming may have an inherent advantage of generating chamber-matched new cardiomyocytes as a potential heart regenerative approach.

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