Similar Datasets
Project description:Zebrafish regenerate heart muscle through division of pre-existing cardiomyocytes. To discover underlying regulation, we assess transcriptome datasets for dynamic gene networks during heart regeneration and identify suppression of genes associated with the transcription factor Tp53. Cardiac damage leads to fluctuation of Tp53 protein levels, concomitant with induced expression of its central negative regulator, mdm2, in regenerating cardiomyocytes. Zebrafish lacking functional Tp53 display increased indicators of cardiomyocyte proliferation during regeneration, whereas transgenic Mdm2 blockade inhibits injury-induced cardiomyocyte proliferation. Induced myocardial overexpression of the mitogenic factors Nrg1 or Vegfaa in the absence of injury also upregulates mdm2 and suppresses Tp53 levels, and tp53 mutations augment the mitogenic effects of Nrg1. mdm2 induction is spatiotemporally associated with markers of de-differentiation in injury and growth contexts, suggesting a broad role in cardiogenesis. Our findings reveal myocardial Tp53 suppression by mitogen-induced Mdm2 as a regulatory component of innate cardiac regeneration.
| S-EPMC7494019 | biostudies-literature
Project description:Tp53 suppression promotes cardiomyocyte proliferation during zebrafish heart regeneration
| PRJNA612190 | ENA
Project description:We compared transcriptional profiles of regenerating zebrafish caudal fins following fin amputation with profiles from uninjured zebrafish caudal fins
2016-04-08 | GSE76564 | GEO
Project description:The adult vertebrate red spotted newt is a champion of regeneration, demonstrating an amazing ability to regenerate damaged organs and tissues back to an uninjured state without the formation of scar or reduction in function. By developing a novel cardiac resection strategy, our group recently demonstrated that newt hearts could morphologically and functionally regenerate, without scarring, within a period of 2-3 months following injury. MicroRNAs (miRs) have been widely publicized as essential post-transcriptional gene regulators in a variety of biological processes, including regeneration. We have conducted a microarray screen for vertebrate miRs, with several candidate miRs showing significant differential expression at important time-points following injury to the newt heart. The newt microRNA expression between uninjured hearts and regenerating hearts, 7 and 21 days post-injury (dpi), was compared by microarray analysis. Three paired samples were analyzed: Uninjured, 7dpi and 21dpi newt hearts. Three arrays were hybridized comparing two-paired samples each time.
2013-09-24 | E-GEOD-44547 | biostudies-arrayexpress
Project description:The human heart's failure to replace ischemia-damaged myocardium with regenerated muscle contributes significantly to the worldwide morbidity and mortality associated with coronary artery disease. Remarkably, certain vertebrate species, including the zebrafish, achieve complete regeneration of amputated or injured myocardium through the proliferation of spared cardiomyocytes. Nonetheless, the genetic and cellular determinants of natural cardiac regeneration remain incompletely characterized. Here, we report that cardiac regeneration in zebrafish relies on Notch signaling. Following amputation of the zebrafish ventricular apex, Notch receptor expression becomes activated specifically in the endocardium and epicardium, but not the myocardium. Using a dominant negative approach, we discovered that suppression of Notch signaling profoundly impairs cardiac regeneration and induces scar formation at the amputation site. We ruled out defects in endocardial activation, epicardial activation, and dedifferentiation of compact myocardial cells as causative for the regenerative failure. Furthermore, coronary endothelial tubes, which we lineage traced from preexisting endothelium in wild-type hearts, formed in the wound despite the myocardial regenerative failure. Quantification of myocardial proliferation in Notch-suppressed hearts revealed a significant decrease in cycling cardiomyocytes, an observation consistent with a noncell autonomous requirement for Notch signaling in cardiomyocyte proliferation. Unexpectedly, hyperactivation of Notch signaling also suppressed cardiomyocyte proliferation and heart regeneration. Taken together, our data uncover the exquisite sensitivity of regenerative cardiomyocyte proliferation to perturbations in Notch signaling.
| S-EPMC3910613 | biostudies-other
Project description:Exercise promotes a set of physiological adaptations known to provide long-term health benefits and it can play an important role in cardioprotection. However, the mechanisms underlying exercise-induced cardiac adaptation are not fully understood. In the present study, we examined cardiac adaptive responses to exercise training in the adult zebrafish and in the context of cardiac regeneration.We found that swimming-induced exercise increased cardiomyocyte proliferation and that this response was also found under regenerating conditions, when exercise was performed either prior to and after ventricular cryoinjury (CI). Exercise prior to CI resulted in a mild improvement in cardiac function and lesion recovery over the non-exercise condition.Transcriptomic profiling of regenerating ventricles in cryoinjured fish subjected to exercise revealed a differential regulation of genes related toregeneration as well as other biological processes potentially involved in the exercise response. Taken together, these results suggest that exercise constitutes a physiological stimulus thatmay help promote cardiomiogenic mechanisms of the vertebrate heart and that the zebrafish exercise model may be useful for evaluating the potential cardioprotective effects of exercise.
2018-10-18 | GSE100892 | GEO
Project description:Single cell sequencing was performed on the adult zebrafish liver, on both uninjured animals, and animals regenerating from hepatocyte ablation.
2023-01-11 | GSE217839 | GEO
Project description:Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse. Here we use this system to show that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and the expression of regulators of cell-cycle progression. Specifically, we show that the gene product of polo-like kinase 1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process.
| S-EPMC2846535 | biostudies-literature
Project description:A transgenic line cmlc2:TRAP was made to express EGFP-fused ribosomal protein L10a (EGFP-L10a) in zebrafish cardiomyocytes. Then ribosome-associated RNAs were immuoprecipitated from uninjured and injured adult cmlc2:TRAP fish to determine the differential expression changes during zebrafish heart regeneration. A nine chip study with cardiomyocyte ribosome associated RNAs purified from three separate isolation of uninjured adult cmlc2:TRAP fish hearts, three separate isolation of 1 day post amupation (dpa) adult cmlc2:TRAP fish hearts, and three separate isolation of 7 dpa adult cmlc2:TRAP fish hearts.
2013-08-01 | E-GEOD-48914 | biostudies-arrayexpress
Project description:Adult zebrafish are capable of regenerating cardiac tissue following ventricular resection within 30 days. We profiled both small RNA and mRNA expression in uninjured (0dpa), 1, 3, 7, 14, 21 and 30 days post amputation to study biological processes orchestrate each stage of regeneration.
2018-05-29 | GSE106884 | GEO