Cardiomyocyte heterogeneity in zebrafish development and regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA662347 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12610268.fastq.gz | Fastqsanger.gz | |||
| SRR12610269.fastq.gz | Fastqsanger.gz | |||
| SRR12610270.fastq.gz | Fastqsanger.gz | |||
| SRR12610271.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Contrary to adult mammals, zebrafish are able to regenerate their heart after cardiac injury. This regenerative response relies, in part, on the endogenous ability of cardiomyocytes (CMs) to dedifferentiate and proliferate to replenish the lost muscle. However, CM heterogeneity and population dynamics during development and regeneration remain poorly understood. Through comparative transcriptomic analyses of the developing and adult zebrafish heart, we identified tnnc2 and tnni4b.3 expression as markers for CMs at early and late developmental stages, respectively. Using newly developed reporter lines for these genes, we investigated their expression dynamics during development and regeneration, and observed interesting expression patterns. tnnc2 reporter lines label most CMs at embryonic stages, and this labeling declines rapidly during larval stages; in adult hearts expression is only detectable in a subset of CMs. Conversely, expression of a tnni4b.3 reporter is initially visible in outer curvature CMs at larval stages, and it is subsequently present in a vast majority of the CMs in adult hearts. Interestingly, we find that the adult CMs labeled by the embryonic reporter display higher levels of Tg(tp1:EGFP) expression, which indicates active Notch signaling. To further characterize this CM population, we performed transcriptomic analysis and found that it expresses genes encoding components of the Notch signaling pathway as well as markers of immature CMs. Moreover, during heart regeneration, proliferating CMs in the injured area activate the embryonic CM reporter. Overall, our findings provide further evidence of cardiomyocyte heterogeneity in the adult zebrafish heart.
2021-05-03 | GSE157662 | GEO
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:Fibroblasts are activated to repair the heart following injury. Fibroblast activation in the mammalian heart leads to a permanent fibrotic scar that impairs cardiac function. In other organisms, such as zebrafish, cardiac injury is followed by transient fibrosis and scar-free regeneration. The mechanisms that drive scarring versus scar-free regeneration are not well understood. Here, we show that the homeobox-containing transcription factor Prrx1b is required for scar-free regeneration of the zebrafish heart as the loss of Prrx1b results in excessive fibrosis and impaired cardiomyocyte proliferation. Through lineage tracing and single-cell RNA sequencing we find that Prrx1b is activated in epicardial-derived cells where it restricts TGFβ ligand expression and collagen production. Furthermore, through combined in vitro experiments in human fetal epicardial-derived cells and in vivo rescue experiments in zebrafish, we conclude that Prrx1 stimulates Nrg1 expression and promotes cardiomyocyte proliferation. Collectively, these results indicate that Prrx1 is a key transcription factor that balances fibrosis and regeneration in the injured zebrafish heart.
2021-09-16 | GSE153170 | GEO
Project description:Ischemic cardiopathy is the leading cause of death in the world, for which efficient regenerative therapy is not currently available. In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue featuring collagen deposition and tissue remodelling with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Due to the lack of genetic lineage tracing evidence, it is not yet clear if new cardiomyocytes arise from existing contractile cells or from an uncharacterised set of progenitors cells. Nonetheless, several genes and molecules have been shown to participate in this process, some of them being cardiomyocyte mitogens in vitro. Though questions as what are the early signals that drive the regenerative response and what is the relative role of each cardiac cell in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts, and identified additional genes the expression of which is differentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative RT-PCR. For a subset of these genes, their expression pattern was analyzed by in situ hybridization and shown to be upregulated in the regenerating area of the heart. The specific role of these new transcripts during zebrafish heart regeneration was further investigated ex vivo using primary cultures of zebrafish cardiomyocytes and/or epicardial cells. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications. In order to study zebrafish heart regeneration, a time course experiment was realized where amputated heart regenerating were compared to control heart. Samples in triplicate were extracted at 1, 3, 5 and 7 days post-amputation.
2010-03-09 | E-GEOD-17993 | biostudies-arrayexpress
Project description:Tp53 suppression promotes cardiomyocyte proliferation during zebrafish heart regeneration
| PRJNA612190 | ENA
Project description:The zebrafish has emerged as a powerful model to study cardiac regeneration; however, the mechanisms by which cardiomyocytes respond to damage by disassembling sarcomeres, proliferating, and repopulating the injured area remain unclear. Here, we show that AP-1 transcription factors play an essential role in regulating the cardiomyocyte response. Using ATAC-Seq, we first find that the cardiomyocyte chromatin accessibility landscape is dynamic following cryoinjury, and that AP-1 motifs are the most highly enriched in regions that gain accessibility during regeneration. Using a cardiomyocyte-specific dominant-negative approach, we show that AP-1 promotes cardiomyocyte proliferation as well as chromatin accessibility at genes regulating sarcomere disassembly and cardiomyocyte protrusion into the injured area. We further find distinct temporal requirements for AP-1 during cardiac regeneration. Altogether, these results indicate that AP-1 plays a key role in the cardiomyocyte response to injury by promoting chromatin accessibility changes, allowing the activation of gene expression programs that support regeneration.
2020-06-10 | GSE130940 | GEO
Project description:For a short period of time in mammalian neonates, the mammalian heart can regenerate via cardiomyocyte proliferation. This regenerative capacity is largely absent in adults. In other organisms, including zebrafish, damaged hearts can regenerate throughout their lifespans. Many studies have been performed to understand the mechanisms of cardiomyocyte de-differentiation and proliferation during heart regeneration however, the underlying reason why adult zebrafish and young mammalian cardiomyocytes are primed to enter cell cycle have not been identified. Here we show the primed state of a pro-regenerative cardiomyocyte is dictated by its amino acid profile and metabolic state. Adult zebrafish cardiomyocyte regeneration is a result of amino acid-primed mTOR activation. Zebrafish and neonatal mouse cardiomyocytes display elevated glutamine levels, predisposing them to amino acid-driven activation of mTORC1. Injury initiates Wnt/β-catenin signalling that instigates primed mTORC1 activation, Lin28 expression and metabolic remodeling necessary for zebrafish cardiomyocyte regeneration. These studies reveal a unique mTORC1 primed state in zebrafish and mammalian regeneration competent cardiomyocytes.
2022-02-15 | PXD011791 | Pride
Project description:By contrast with mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of spared cardiomyocytes. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration through paracrine effects and as a multipotent cell source, and has received recent attention as a target in cardiac repair strategies. While it is recognized that epicardium is required for muscle regeneration and itself has high regenerative potential, the extent of cellular heterogeneity within epicardial tissue is largely unexplored. In this study, we performed transcriptome analysis on dozens of epicardial lineage cells purified from zebrafish harboring a transgenic reporter for the pan-epicardial gene tcf21. Hierarchical clustering analysis suggested the presence of at least three epicardial cell subsets defined by expression signatures. We validated many new pan-epicardial and epicardial markers by alternative expression assays. Additionally, we explored the function of the scaffolding protein and main component of caveolae, caveolin-1 (cav1), which was present in each epicardial subset. In BAC transgenic zebrafish, cav1 regulatory sequences drove strong expression in ostensibly all epicardial cells and in coronary vascular endothelial cells. Moreover, cav1 mutant zebrafish generated by genome editing showed grossly normal heart development and adult cardiac anatomy, but displayed profound defects in injury-induced cardiomyocyte proliferation and heart regeneration. Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration. Deep sequencing of isolated single epicardial cells
2015-12-15 | E-GEOD-75583 | biostudies-arrayexpress
Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.
2020-07-13 | PXD016235 | Pride
Project description:Unlike human hearts, zebrafish hearts efficiently regenerate after injury. Regeneration is driven by the strong proliferation response of its cardiomyocytes to injury. In this study, we show that active telomerase is required for cardiomyocyte proliferation and full organ recovery, supporting the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction. Heart transcriptomes of WT and telomerase defective adult zebrafish animals were profiled by RNASeq, in control conditions and 3 days after heart cryoinjury.
2015-08-06 | E-GEOD-71755 | biostudies-arrayexpress