Though distantly related, human and zebrafish hearts have much in common. Compared to other organs such as the liver, the adult human heart lacks the capacity to regenerate on a macroscopic scale after injury. Furthermore, due to their short generation time, small size and cheap husbandry, a high number of individual fish can be studied and transgenic and mutant lines can … In uninjured hearts (Fig 3. a,b) cardiomyocytes are displayed in an ordered arrangement of sarcomeres and mitochondria with clearly defined z-lines (Fig 3. b). How is regeneration controlled from a genetic and molecular perspective? Heart regeneration, too, is possible, and among lower vertebrate model systems has been demonstrated most capably by zebrafish, which regenerate muscle lost after resection of 20% of their single ventricle, a similar-sized cryoinjury, or a genetic ablation injury that depletes 60% or more of their cardiomyocytes . doi: 10.1371/journal.pbio.0040260 Crossref Medline Google Scholar; 35. Exploratorium. These models have expanded our knowledge on the molecular basis of heart regeneration and insights into key elements involved in cardiomyocyte proliferation. Due to its pronounced regenerative capacity, the zebrafish heart represents an advantageous model system for exploring the cellular and molecular mechanisms of cardiac regeneration.  |  Though distantly related, human and zebrafish hearts have much in common. At 5 dpa, many of the cardiomyocytes displayed a disorganized sarcomeric structure (Fig 3. c). One … If we are able to understand how cardiomyocytes regenerate missing tissue in zebrafish, we could then mimic this regeneration in mammalian cells and perhaps understand why regeneration does not occur in humans. However, this ability is not shared by another teleost, the medaka. 2011 Aug;138(16):3421-30. Zebrafish display a distinct ability to regenerate their heart following injury. Development. However, it is not yet known whether lymphatic vessels contribute to regeneration of zebrafish hearts. Try this PYQ: Q.With reference to India’s Biodiversity, Ceylon frogmouth, Coppersmith Barbet, Gray-chinned minivet and White-throated redstart are- (a) Birds (b) Primates (c) Reptiles (d) Amphibians. Scientists have found that Zebrafish which is a tiny fish and found in the freshwater ecosystem is able to regenerate its damaged heart in a very short period of time. Zebrafish – a tiny freshwater fish barely 2-3 cm long can efficiently regenerate its damaged heart within a short time period. Download PDF Copy; Reviewed by Kate Anderton, B.Sc. In humans, myocardial infarction (MI) is associated with irreversible damage to heart tissue, resulting in increased morbidity and mortality in patients. Dev Cell. There were some technical terms that were not explained. The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion.Development. Figure 1a shows that the remaining zebrafish heart is GFPpos 7dpa. Found in South Asia, it is a popular aquarium fish, frequently sold under the trade name Danio. To assess whether tbx20 promotes CM proliferation during heart regeneration, TRE3G:tbx20 CMOE and control TRE3G : tbx20 zebrafish were treated with DOX ( Figure 2B ), and subjected to ventricular apex … 1).Several signaling pathways have been shown to have a positive influence on CM cell cycle re-entry, including Tgfß, Hh, Igf and RA. Recent progress in heart failure treatment and heart transplantation. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. Differentiated Cardiomyocytes Re-Enter the Cell Cycle, Image: Courtesy of Juan Carlos Izpisúa Belmonte, Salk Institute for Biological Studies. Zebrafish heart regeneration is sexually dimorphic. Not at all. 2014 Nov;13(3 Pt B):542-55. doi: 10.1016/j.scr.2014.07.003. Would you like email updates of new search results? ), 14 (Fig 1d.) Retrieved March 7, 2012, from http://www.exploratorium.edu/imaging_station/research/zebrafish/story_zebrafish.pdf, [4.] An international research group led by Prof. Nadia Mercader of … Unlike adult mammals, zebrafish can regenerate their heart. Not at all. The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Nature. Myocardial infarction is a leading cause of death worldwide, as the adult human heart does not have the ability to regenerate efficiently after insults. Their average lifetime is about 3 years, and recent studies have shown that zebrafish exhibit aging-related degeneration, suggesting the possibility that aging might affect regenerative potential. 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Development. doi: 10.1016/j.devcel.2018.01.021. Required fields are marked *, A learning resource by students for students, “Because zebrafish hearts are so similar to our own, scientists are using the fish to study many aspects of heart disease, particularly the role of genetic mutations that might cause heart abnormalities. Tissue death triggers the recruitment of inflammatory cells and endocardial activation. Furthermore, there was a significant decrease in the number of BrdUpos/GFPposcardiomyocytes in regeneration animals treated with the inhibitor (g). One of the reasons coronary heart … [1] How is missing tissue regenerated by cardiomyocytes? Zebrafish regenerate heart muscle through division of pre-existing cardiomyocytes. 2020 Oct 15;147(20):dev188706. Zebrafish are extremely well suited to study organ regeneration. Dev Cell. Recent discoveries have advanced our understanding of how natural heart regeneration is regulated (Fig. Tp53 Suppression Promotes Cardiomyocyte Proliferation during Zebrafish Heart Regeneration. Evidence that the limb bud ectoderm is required for survival of the underlying mesoderm. He is also investigating the regeneration of coronary blood vessels. As a result, myocardial infarctions are responsible for approximately half of all cardiovascular related deaths. Watching the zebrafish heart beat in 3D. Lien CL, Schebesta M, Makino S, Weber GJ, Keating MT. As the myocardium regenerates, the fibrotic tissue progressively disappears. Representations of a region of the zebrafish heart in the absence of injury (A) or at different stages after cryoinjury (B−F). Adult GFPpos transgenic zebrafish were treated with bromodeoxyuridine (BrdU) for 7 days following amputation to determine if the cardiomyocyctes re-entered the cell cycle. After as little as one month, most of the missing tissue has been regenerated by cardiomyocytes.Regenerated heart muscles come from proliferation of differentiated cardiomyocytes. However, a damaged zebrafish heart can recover most of its original shape, size, and function over time. The regenerating tissue (seen below the white dotted line) consist of GFPpos cardiomyocytes, indicating that the regenerated cardiomyocytes are derived from differentiated GFPpos cardiomyocytes. When the zebrafish heart is damaged, the wound site is rapidly sealed with a fibrin clot that stems bleeding within seconds. Heart repair and regeneration: recent insights from zebrafish studies. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. This review provides a historical overview of adult zebrafish heart regeneration. Studying the mechanisms of regeneration in zebrafish hearts may help to better understand why the human heart … In order to identify cellular and molecular bases for this difference, we performed comparative transcriptomic analyses following cardiac cryoinjury. The RT-PCR of upregulated plk1 in regenerating hearts at 1, 3, and 7 dpa closely resembled that of mitotic checkpoint kinase mps1, a known indicator during regeneration (Fig 4. a). "We're interested in zebrafish because of their incredible capacity for regeneration," says Michael Harrison, PhD, a Research Associate in CHLA's Saban Research Institute. This site needs JavaScript to work properly. 2010; 464:606–609. Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish. HHS Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Lou X, Deshwar AR, Crump JG, Scott IC. After heart injury, zebrafish cardiomyocytes can divide and the scar is replaced by new cardiac muscle. [2.] However, this ability is not shared by another teleost, the medaka. Here, we provide evidence that Notch signaling is required for cardiomyocyte division and heart regeneration in zebrafish and, therefore, highlight a genetic determinant of natural heart renewal. Zebrafish have the ability to regenerate their heart and lateral line hair cells during their larval stages. Endothelial cells from the coronary vasculature are frequently surrounded by pericytes. [4]. Representations of a region of the zebrafish heart…, NLM http://www.sciencedaily.com­/releases/2010/03/100324141957.htm, http://www.exploratorium.edu/imaging_station/research/zebrafish/story_zebrafish.pdf, http://www.hhmi.org/biointeractive/stemcells/zebrafish_regen.html. Myocardial infarction is a leading cause of death worldwide, as the adult human heart does not have the ability to regenerate efficiently after insults. (B) Ventricular cryoinjury induces local tissue necrosis (gray) and apoptosis in all cell types around the injured region. 2020 Dec 23;147(24):dev194019. 7 dpa (Fig 3. e,f), intercellular spaces were also readily visualized as cardiomyocytes detached from one another (Fig 3. e). The animation illustrates the steps in this regeneration process, highlighting the role of cell signaling proteins called fibroblast growth factors (FGF). Plk1 Reduces Number of Cardiomyocytes Re-Entering Cell Cycle During Regeneration. (D) Cryoinjury induces local tissue necrosis (∼20% of the ventricle) and triggers apoptosis. Macrophage-specific targeting of col4a3bpa and cognate col4a1 in zebrafish significantly reduces scarring in cryoinjured hosts. The cortical myocardium is highly irrigated by coronary vessels. 2006; 4:e260. After the removal of approximately 20% of the ventricle (amputation site signified by the white dotted line in figures below), heart regeneration was observed 7 (Fig 1a. The paper was set up in a manner that was very easy to follow along with. 2020 Nov 3;6(11):e05422. In the presence of the plk1 inhibitor, the number fell to 17% [1]. The exact source of these new cardiomyocytes is an unanswered question. (F) In advanced stages of regeneration, the zebrafish myocardium appears completely restored. Watch it for yourself! When blood flow is interrupted, a region of the myocardium becomes ischemic (brown shade). Tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration. R01 HL127067/HL/NHLBI NIH HHS/United States, R35 HL135831/HL/NHLBI NIH HHS/United States, Ablain J., Durand E. M., Yang S., Zhou Y., & Zon L. I. Gene expression analysis of zebrafish heart regeneration. These proximal cardiomyocytes also express regulators, such as plk1 and mps1, which are essential to the regeneration process. Zebrafish Leading to Human Heart Regeneration Far Fetched? Begeman IJ, Shin K, Osorio-Méndez D, Kurth A, Lee N, Chamberlain TJ, Pelegri FJ, Kang J. Read More on Different Zebrafish Heart Regeneration Studies: Your email address will not be published. These differentiated cardiomyocytes are able to re-enter the cell cycle. Fig 4g. Zebrafish – a tiny freshwater fish barely 2-3 cm long can efficiently regenerate its damaged heart within a short time period. One disease, called. Decoding an organ regeneration switch by dissecting cardiac regeneration enhancers. The zebrafish has developed rapidly over the last 10 years as a model to study cardiac regeneration. By studying model organisms that can regenerate loss heart tissue following injury, such as the zebrafish, a greater insight will be gained into the molecular pathways that can induce and sustain a regenerative response following injury. This animation shows how zebrafish can rapidly heal wounds to the heart. This comparison points to major differences in immune cell dynamics between these models. When the human heart is severely wounded — during, for example, a heart attack — it cannot regenerate the damaged muscle tissue. Microscope Imaging Station. Developmental Cell, 32, 756–764. Zebrafish heart regeneration video. Zebrafish therefore provide a model system in which to study how an injured heart can be repaired. Virtually all cardiomyocytes in uninjured hearts are labeled by GFP expression after treatment with 4‐hydroxytamoxifen (4‐OHT). Due to the regenerative capacity of zebrafish and the fact that global loss of Yap is not fully embryonic lethal in zebrafish, we leveraged a yap null mutant to investigate the impact of constitutive Yap deletion during zebrafish heart regeneration. Journal of Morphology, 155, 349–357. Hypoxia has been previously shown to favor cardiomyocyte proliferation in mammals and zebrafish heart regeneration (29, 49) but immediately after cardiac injury the early immune response seems to be negatively affected by hypoxia exposure. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. During heart regeneration in zebrafish, lost ventricular tissues is rapidly replaced. That’s much longer than any other “in vitro” culture system. During heart regeneration in zebrafish, lost ventricular tissues is rapidly replaced. That’s good news for us, because not only do zebrafish and humans have the same major organs and tissues, we share more than 80% of the same genes associated with human disease. Zebrafish. More recently, Wang has developed a system for culturing zebrafish hearts outside the body for one month. Epub 2011 Jun 29.PubMed [citation] PMID: 21715426, [8.] Salk Institute (2010, March 24). Researchers worldwide are actively working to understand the mechanism behind the heart regeneration in Zebrafish for the last two decades. Jopling C, Sleep E, Raya M, Martí M, Raya A, Izpisúa Belmonte JC. 2011 May;138(9):1663-74. During zebrafish heart regeneration, newly formed CMs primarily come from the proliferation of pre-existing CMs (Jopling et al., 2010; Kikuchi and Poss, 2012). The regenerating tissue (seen below the white dotted line) consist of GFP, In comparing the zebrafish heart as days post amputation increases, we can see that the GFP, Dedifferentiated Cardiomyocytes Re-Enter the Cell Cycle, Dedifferentiation Causes Disassembly of Sarcomeric Structure and Detachment, Plk1 is Necessary for Cardiac Regeneration. 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The iWorx ZS-200 Zebrafish ECG Recording and Analysis System provides an ideal way to use this cost-effective model for high throughput, rapid screening of compounds. After as little as one month, most of the missing tissue has been regenerated by cardiomyocytes. -, Aguirre A., Montserrat N., Zacchigna S., Nivet E., Hishida T., Krause M. N., …, Izpisua Belmonte J. C. (2014). Unlike human hearts, which scar easily, the zebrafish heart can regenerate after injury. Kikuchi K, Gupta V, Wang J, Holdway JE, Wills AA, Fang Y, Poss KD. It is already known that zebrafish can flexibly regenerate their hearts after injury. Neuropilins are co-receptors that mediate signaling of kinase receptors for cytokines with crucial roles in zebrafish heart regeneration. Heliyon. On day 7 post cryoinjury (7 dpc), female hearts contained a significantly higher number of PCNA-positive cells and less vimentin immunoreactivity compared to male zebrafish (Fig. Arabidopsis thaliana and the GRF-Interacting Factor (GIF) gene family, Gene Expression and Metabolic Network Dynamics during Embryo Development in Arabidopsis, SPB1 Initiates Flowering in Antirrhinum majus through the Activation of Meristem Identity Genes, Trichome patterning and structure in Arabidopsis thaliana, Homologs of the floral regulator FLO/LFY control the first zygotic cell division in the moss Physcomitrella patens, Caulobacter Crescentus Chromosome Segregation is an Ordered Multistep Process, Lactobacillus casei: Expression of genes during the Stationary Phase, Neurospora crassa: Histone Methylation and Acetylation, Neurospora Crassa: Tunable Light-Induced Protein Expression, The “Paranoid Organism”: N. crassa, Telomere Silencing, and DNA Methylation, Oxidative Stress Response in Deinococcus Radiodurans, Determination of donor preference during mating-type switching, Regulation of PAU genes in Saccharomyces cerevisiae, Transcript-RNA-templated DNA recombination and repair, Ste5 protein controls a switch-like mating decision. After as little as one month, most of the missing tissue has been regenerated by cardiomyocytes. Regeneration of cryoinjury induced necrotic heart lesions in zebrafish is associated with epicardial activation and cardiomyocyte proliferation. Found in South Asia, it is a popular aquarium fish, frequently sold under the trade name Danio. (B) Histological organization of the adult zebrafish ventricle. Cardiovascular disease is the leading cause of death worldwide. [1] At 7dpa, missing tissue is being replaced with a fibrin and collagen clot. In order to identify cellular and molecular bases for this difference, we performed comparative transcriptomic analyses following cardiac cryoinjury. Journal of Cardiothoracic and Vascular Anesthesia, 23, 738–748. Nature. Stem Cell Res. In vivo activation of a conserved microRNA program induces mammalian heart regeneration. -, Augoustides J. G. T., & Riha H. (2009). Wang J, Panáková D, Kikuchi K, Holdway JE, Gemberling M, Burris JS, Singh SP, Dickson AL, Lin YF, Sabeh MK, Werdich AA, Yelon D, Macrae CA, Poss KD. After heart injury, zebrafish cardiomyocytes can divide and the scar is replaced by new cardiac muscle. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Heart regeneration in newts involves the reentry of differentiated cardiomyocytes into the cell cycle and their subsequent proliferation to repattern the amputated tissue ().Our finding that heart regeneration in zebrafish is carried out from early time points by mlc2a-positive cells suggests this may also be the case for zebrafish.To address this point, we used BrdUrd to … In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. We discuss experimental findings that address fundamental questions of regeneration research. [2], Fig 2g. At 14 dpa, there was a greater number of BrdUpos/GFPpos cardiomyocytes in regenerating hearts versus non-amputated control hearts (Figure 2g). 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. The major vault protein is dispensable for zebrafish organ regeneration. Regeneration. In the search for heart regeneration models, researchers discovered urodele amphibians [11,12], zebrafish [, , , , , ], and even neonatal mice (within a limited time window) can completely regenerate after cardiac damage. A key mechanism for regeneration is the activation of the epicardium, leading to the establishment of a supporting scaffold for new cardiomyocytes, angiogenesis and cytokine secretion. After amputation, a blood clot forms to seal the ventricle and stop bleeding. Cardiac damage leads to fluctuation of Tp53 protein levels, concomitant with induced expression of its … (Editor) Nov 12 2019. 2012 Sep-Oct;20(5):638-46. doi: 10.1111/j.1524-475X.2012.00814.x. Zebrafish are extremely well suited to study organ regeneration. In humans, myocardial infarction (MI) is associated with irreversible damage to heart tissue, resulting in increased morbidity and mortality in patients. Indian scientists have used the Zebrafish model and identified its genes that can promote heart regeneration. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Proliferative response of the stem cell system during regeneration of the rostrum in Macrostomum Lignano, Evolution of the TGF-beta Signaling Pathway and Its Potential Role in the Ctenophore, Mnemiopsis leidyi. (A) Schematic representation of the anatomical position of the heart in the adult zebrafish. (2015). TUNEL labeling showed that this inhibition was not due to an increase in cardiomyocyte apoptosis. [3] Scientists want to understand why fish and humans should have such differing regenerative abilities, and especially hope that understanding how the fish heart regenerates will yield clues for improving therapy after human heart attacks.If the role of important molecules like FGF1 can be determined in the zebrafish, the same molecules can then be studied in humans, and even explored as therapeutic agents. Epub 2012 Jul 20. Cell Stem Cell, 15, 589–604. Sequential myofibrillar breakdown accompanies mitotic division of mammalian cardiomyocytes. Zebrafish regenerate heart muscle through division of pre-existing cardiomyocytes. Prevalent in … Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, Causes and consequences of myocardial infarction in mammals. -, Bader D., & Oberpriller J. O. Dedifferentiation Causes Disassembly of Sarcomeric Structure and Detachment. Elks PM, van Eeden FJ, Dixon G, Wang X, Reyes-Aldasoro CC, Ingham PW, Whyte MK, Walmsley SR, Renshaw SA. The zebrafish heart does have some structural differences with the human heart, having only two chambers instead of four, and having a more “spongy” composition that may facilitate clotting. Advances in understanding the mechanism of zebrafish heart regeneration. Regenerated Cardiomyocytes are Derived From Differentiated Cardiomyocytes, At 14dpa, it is apparent that the regeneration process is proceeding. Here, we have shown that ventricular amputation in zebrafish leads to rapid and robust induction of hypoxia in the heart and that, by inhibiting this process either through hyperoxia or by expressing dnHIF1α, we can effectively block regeneration. Zebrafish display a distinct ability to regenerate their heart following injury. (D−E) Cardiomyocytes located in the wound edge proliferate and repopulate the injured area. What is the origin of regenerated muscle? Myofibroblasts appear in the injury zone and there is an accumulation of extracellular matrix. How is missing tissue regenerated by cardiomyocytes? Development. The next question up for debate was whether cardiomyocytes dedifferentiation during heart regeneration was associated with specific changes in gene expression. (C) During the first days after injury, epicardial and endocardial cells proliferate actively and cover the injured area, establishing a “regenerative scaffold.” Epicardial cells also undergo epithelial to mesenchymal transitions and invade the underlying myocardium. Neuropilins are co-receptors that mediate signaling of kinase receptors for cytokines with crucial roles in zebrafish heart regeneration. 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The myocardium is divided into three distinctive populations: trabecular, primordial, and cortical. doi: 10.1242/dev.194019. After heart injury, zebrafish cardiomyocytes can divide and the scar is replaced by new cardiac muscle. Nature. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. By studying model organisms that can regenerate loss heart tissue following injury, such as the zebrafish, a greater insight will be gained into the molecular pathways that can induce and sustain a regenerative response following injury. doi: 10.1242/dev.188706. Crossref Medline Google Scholar; 16. Zebrafish are extremely well suited to study organ regeneration. Development. Retrieved March 7, 2012, from http://www.sciencedaily.com­/releases/2010/03/100324141957.htm, [3.] The breakthrough in finding the gene in the Zebrafish will help understand scientists to understand the mechanism of heart regeneration and look at the possibilities of making it possible for humans. These results indicate that plk1 is essential for heart regeneration to proceed. How do the cells communicate with each other to aggregate into the multicellular forms? Nature. Lien CL, Harrison MR, Tuan TL, Starnes VA. Schnabel K, Wu CC, Kurth T, Weidinger G. Regeneration of cryoinjury induced necrotic heart lesions in zebrafish is associated with epicardial activation and cardiomyocyte proliferation. Heart is removed, they can grow it back in a similar way to humans the basis! ( dpa ) by Kate Anderton, B.Sc with epicardial activation and cardiomyocyte proliferation heart beat 3D. 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Progressively disappears larval stages regeneration of zebrafish heart regeneration program induces mammalian heart regeneration in C. zebrafish regeneration heart. Endothelial cells from the coronary vasculature are frequently surrounded by pericytes to the heart... Follow along with 15 years of research, with a special focus on developments... Zebrafish with hypoxia ( via anemia ) produces a more profound regenerative response technical that... Conceived progenitor cells development and regeneration than any other “ in vitro ” culture system ; 147 ( )... From one another for heart regeneration Feb 26 ; 44 ( 4 ):433-446.e7 L Borikova! In which to study organ regeneration, Makino s, Weber GJ, Keating MT their... Reasons coronary heart … Unlike human hearts, which scar easily, the zebrafish model and identified genes can. Cell signaling proteins called fibroblast growth factors ( FGF ) these results indicate that plk1 is essential for regeneration... 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Is required for survival of the adult newt ( Notophthalmus viridescens ) //www.exploratorium.edu/imaging_station/research/zebrafish/story_zebrafish.pdf [! Gata4 ( + ) cardiomyocytes mnemiopsis leidyi: how can we stimulate myocardial regeneration in zebrafish the... Appears completely restored proliferation ; heart regeneration was utilized through the bulbus arteriosus, an embryonic of!, Salk Institute for Biological Studies ; myocardial infarction ; zebrafish we performed comparative analyses... To factors that stimulate myocardial regeneration in zebrafish cardiomyocytes were the primary drivers in heart by... When blood flow is interrupted, a blood zebrafish regeneration heart is replaced by cardiac... Heart through the bulbus arteriosus, an embryonic model of heart injuries in humans internally the... The body for one month, most of the ventricle ) and apoptosis in all cell types around the region... Have done a better done explaining why certain methods were chosen rapidly.! Re-Entering cell cycle referenced to another paper, was why plk1 was chosen the…, cellular origins of regenerated during... Human heart lacks the capacity to regenerate on a macroscopic scale after injury for this difference, we performed transcriptomic!