Zebrafish heart regeneration at 3 days post amputation (dpa)
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ABSTRACT:
PROVIDER: PRJNA828542 | ENA |
REPOSITORIES: ENA
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Project description:Amputation of heart tissue followed by regeneration of the heart. Samples were taken at 0 hpa (hours post-amputation), 6 hpa, 12 hpa, 24 hpa, 3 dpa and 5 dpa.
2008-09-05 | E-MEXP-1239 | biostudies-arrayexpress
Project description:Zebrafish caudal fin regeneration is an established model to study tissue regeneration. In order to identify novel molecular signaling pathways critical for regeneration, we developed a rapid throughput in vivo regeneration assay. We screened a 2000 member structurally diverse small molecule library, followed by assessment of regenerative progression at three days post amputation. A cluster of glucocorticoids was identified among the âpositive hitsâ. To identify the molecular targets of the activated glucocorticoid receptor, microarray analysis was performed using RNA isolated from the regenerates of control and glucocorticoid exposed zebrafish. We identified 673 transcripts that were differentially regulated. The level of expression and spatial expression pattern of select genes were completed by qPCR and by in situ hybridization, respectively. Altogether, these studies demonstrate the power of chemical genetics to identify chemical probes and their targets which will provide a path towards defining conserved regenerative pathways. Experiment Overall Design: The caudal fin of zebrafish larvae at 2days post fertilization were amputated and exposed to vehicle control alone or Beclomethasone . Regenerating fins were isolated at 1days post amputation. Three replicates were collected at each time point. 150 fins were pooled to comprise one replicate.
2009-02-08 | E-GEOD-10766 | biostudies-arrayexpress
Project description:Adult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial would cap over the amputation site by 12 hours post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were i.p. injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3 and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b. Keywords: Time course and TCDD exposure response
2006-03-20 | GSE3667 | 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:Adult zebrafish, in contrast to mammals, are able to regenerate their hearts in response to injury or experimental amputation. Our understanding of the cellular and molecular bases that underlie this process, although fragmentary, has increased significantly over the last years. However, the role of the extracellular matrix (ECM) during zebrafish heart regeneration has been comparatively rarely explored. Here, we set out to characterize the ECM protein composition in adult zebrafish hearts, and whether it changed during the regenerative response. For this purpose, we first established a decellularization protocol of adult zebrafish ventricles that significantly enriched the yield of ECM proteins. We then performed proteomic analyses of decellularized control hearts and at different times of regeneration. Our results show a dynamic change in ECM protein composition, most evident at the earliest (7 days post-amputation) time-point analyzed. Regeneration associated with sharp increases in specific ECM proteins, and with an overall decrease in collagens and cytoskeletal proteins. We finally tested by atomic force microscopy that the changes in ECM composition translated to decreased ECM stiffness. Our cumulative results identify changes in the protein composition and mechanical properties of the zebrafish heart ECM during regeneration.
2019-08-26 | PXD010092 | Pride
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.
2015-11-05 | GSE74494 | 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:Adult zebrafish hearts have the ability to regenerate. The roles of non-myocytes in this process have remained elusive. Here, we have performed 2 scRNAseq experiments on interstitial cells. Experiment 1 (E1) included interstitial cells obtained from uninjured, regenerating (3 days, 7 days and 14 days post-apical amputation). Experiment 2 (E2) included cells from uninjured, sham-operated (abdomen opened) and regenerating (3 days post-amputation) with and without MMP inhibitor (NSC40520) treatment. Cells were obtained by heart dissection followed by enzymatic dissociation and FACS sorting of single, viable nucleated cells.
2022-03-01 | E-MTAB-10643 | biostudies-arrayexpress
Project description:Purpose: Investigate the transcriptomic landscape throughout the time course of murine digit regeneration after level-dependent amputation. Methods: The terminal phalanx bone of hind limb digits was subjected to either a distal amputation (25% bone length loss) or proximal amputation (65% bone length loss). Total RNA was isolated from bone and fibrous tissues distal to the distal interphalangeal joint at 12, 14, and 21 days post-amputation (DPA). mRNA library was sequenced using Illumina HiSeq 3000. Trimmed reads were aligned to the mouse genome mm10 and batch-corrected. Results: A limb-specific developmental signaling pathway is transiently upregulated at 14 DPA after distal amputation, corresponding with regeneration of digit tip tissues. Absence of a limb-specific pathway after proximal amputation corresponded with minimal regeneration and fibrotic scarring. Conclusions: Digit regeneration is a level-dependent and spatiotemporally controlled process, with distal and proximal amputations showing significant differences in gene expression and tissue regrowth over time.
2020-06-10 | GSE131078 | GEO
Project description:The study compares gene expression profile at 20 days post amputation of the zebrafish ventricular heart between dusp6 mutant and WT siblings.
2018-02-18 | GSE90595 | GEO