Similar Datasets
Project description:Transcriptomics of zebrafish cardiac valve regeneration
| PRJNA563669 | ENA
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:We used a cardiac-specific tamoxifen-dependent Gal4-ERT2/UAS model to achieve uniform but conditionally regulated expression of the oncogene HRASG12V in zebrafish cardiomyocytes. We found that the inhibition of TOR signaling using rapamycin treatment counteracts neoplasic growth. We analyse the transcriptome of neoplasic ventricles after exposure to DMSO and rapamycin and we applied bioinformatic analysis to determine common and distinctive molecular signatures of neoplasia versus regeneration of the heart.
2022-09-05 | GSE191324 | GEO
Project description:Recent findings have highlighted the complex role of inflammation in zebrafish heart regeneration, demonstrating that while inflammation is essential for initiating transient fibrosis and tissue repair, chronic inflammation and unresolved fibrosis could impede full regenerative recovery. In this study, we identified the nuclear receptor Nr4a1 as a critical regulator of this regenerative process in zebrafish. Loss of Nr4a1 function led to a prolonged and excessive inflammatory response, disrupted neutrophil migration, delayed fibrin clearance, and ultimately impaired heart regeneration. Transcriptome-wide RNA-seq analysis at different injury stages revealed molecular disruptions associated with dysregulated inflammation and fibrosis in Nr4a1 mutants. Notably, partial inhibition of the pro-inflammatory cytokine Tnf-α rescued heart regeneration in the nr4a1 mutants, highlighting the therapeutic potential of modulating inflammation. Our findings suggest that Nr4a1 plays a crucial role in orchestrating the immune response during heart regeneration and may serve as a valuable target for enhancing cardiac repair following injury.
2024-12-31 | GSE276850 | 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.
2010-02-25 | GSE17993 | GEO
Project description:The importance of regenerative potential of cardiac stem/progenitor cells (CSCs) after acute myocardial infarction (AMI) has been emphasized in the last decade. Several studies have demonstrated that this cell population has a relevant role in myocardial repair, supported by the establishment of a paracrine cross-talk between CSCs and the injured tissue. However, the majority of current in vitro strategies to study these cells fails to include important modulators of CSC activity, such as the paracrine effect of cardiomyocytes (CMs) and the physicochemical changes occurring in tissue during Ischemia/Reperfusion (I/R) injury. In this work, we established the first human in vitro heterotypic model of myocardial I/R injury with human CSCs (hCSCs) and human induced pluripotent cell-derived cardiomyocytes (hiPSC-CMs) using transwell inserts. hCSCs response to I/R was characterized using advanced whole proteomic mass spectrometry-based tools that allowed us to propose new pathways in hCSCs regenerative process, including: cell cycle regulation inhibition, proliferation through EGF signaling, gluthathione-mediated reactive oxygen species detoxification, and signaling through several paracrine growth factors. The model established in this work contributes with new insights regarding hCSC biology in response to AMI and provides an important tool to study and modulate molecular mechanisms involved in the regenerative potential of CSCs.
2019-02-18 | PXD008156 | Pride
Project description:Spinal cord injury triggers a strong innate inflammatory response in both non-regenerative mammals and regenerative zebrafish. Neutrophils are the first immune population to be recruited to the injury site. Yet, their role in the repair process, particularly in a regenerative context, remains largely unknown. Here, we show that, promoting neutrophil inflammation resolution by inhibiting Cxcr4 boosts cellular and functional regeneration. Neutrophil-specific RNA-seq analysis reveals an enhanced activation state that correlates with a transient increase in tnf-a expression in macrophage/microglia populations. Conversely, blocking neutrophil recruitment through Cxcr1/2 inhibition diminishes the presence of macrophage/microglia at the injury site and impairs spinal cord regeneration. Altogether, these findings provide new insights into the role of neutrophils in spinal cord regeneration, emphasizing the significant impact of their immune profile on the outcome of the repair process.
2024-07-03 | GSE271113 | GEO
Project description:Cardiovascular disease is the leading cause of morbidity and mortality in the Western world due to a limited regenerative capacity. In lieu of new muscle synthesis, the human heart replaces necrotic tissue with deposition of a non-contractile scar. In contrast, the adult zebrafish is endowed with a remarkable regenerative capacity, capable of de novo cardiomyocyte (CM) creation and scar tissue resolution when challenged with an acute injury. In these studies, we examined the contributions of the dynamically regulated microRNA, miR-101a, during adult zebrafish heart regeneration. We demonstrate that miR-101a expression is rapidly depleted within 3 days post-amputation (dpa) but is highly upregulated by 7-14 dpa, before returning to uninjured levels at the completion of the regenerative process. Employing heat-inducible transgenic strains and antisense oligonucleotides, we demonstrate that decreases in miR-101a levels at the onset of cardiac injury enhanced CM proliferation. Interestingly, prolonged suppression of miR-101a activity stimulates new muscle synthesis but with defects in scar tissue resolution. Upregulation of miR-101a expression between 7-14 dpa is critical to stimulate remodeling of the scar. Through a series of studies, we identified the proto-oncogene, fosab (cfos) as a potent miR-101a target gene, stimulator of CM proliferation, and inhibitor of scar tissue remodeling. Importantly, combinatorial depletion of fosab and miR-101a activity rescued defects in scar tissue resolution mediated by miR-101a inhibition alone. In summation, our studies indicate that the precise temporal modulation in the miR-101a/fosab genetic axis is critical for coordinating CM proliferation and scar tissue resolution during zebrafish heart regeneration. Pooled cardiac samples from uninjured and regenerating (6hpa) adult fish in biological triplicate.
2015-11-05 | E-GEOD-74494 | biostudies-arrayexpress
Project description:The aim of the study is to investigate the endocrinogenesis process in zebrafish pancreas during normal development and regenerative condition.
2023-03-14 | GSE226841 | GEO
Project description:We dissected cell type diversity in the regenerating zebrafish heart by single cell transcriptomics and discovered a high complexity of cell types specifically among the non-muscle cells. Based on spatiotemporal information, we systematically identified potential cellular regulators of cardiomyocyte regeneration, including several fibroblast-like cell types that express pro-regenerative factors. We used high-throughput lineage tracing12 to determine the origin of cell types in the regenerative niche. We showed that the endocardium, like the epicardium, gives rise to several distinct fibroblast cell types, and found that this process is regulated by Wnt signalling. Our results reveal an unexpected functional specialization of fibroblast cell types during the regenerative process.
2022-05-06 | GSE159032 | GEO