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Transcriptome analysis of heart regeneration in adult zebrafish

ABSTRACT: After heart injury, adult zebrafish can perfectly regenerate its heart without any scar tissue left. We performed 100bp*2, paired-end, strand-specific, polyA-positive RNA-seq on hearts from 2 group of adult zebrafish, in which one was sham group and the other 7 days after heart tip amputation (7dpa). We found pathways involving hydrogen peroxidate related functions significantly up-regulated in 7dpa group, indicating its role in heart regeneration. RNA-seq: hearts from sham or 7dpa adult zebrafish

ORGANISM(S): Danio rerio

SUBMITTER: Shouyu Yan

PROVIDER: E-GEOD-50203 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Hydrogen peroxide primes heart regeneration with a derepression mechanism.

Han Peidong P Zhou Xiao-Hai XH Chang Nannan N Xiao Cheng-Lu CL Yan Shouyu S Ren He H Yang Xin-Zhuang XZ Zhang Mei-Ling ML Wu Qing Q Tang Boyang B Diao Ju-Peng JP Zhu Xiaojun X Zhang Chuanmao C Li Chuan-Yun CY Cheng Heping H Xiong Jing-Wei JW

Cell research 20140815 9

While the adult human heart has very limited regenerative potential, the adult zebrafish heart can fully regenerate after 20% ventricular resection. Although previous reports suggest that developmental signaling pathways such as FGF and PDGF are reused in adult heart regeneration, the underlying intracellular mechanisms remain largely unknown. Here we show that H2O2 acts as a novel epicardial and myocardial signal to prime the heart for regeneration in adult zebrafish. Live imaging of intact hea ...[more]

PMID: 25124925

Similar Datasets

Transcriptome analysis of heart regeneration in adult zebrafish

Project description:After heart injury, adult zebrafish can perfectly regenerate its heart without any scar tissue left. We performed 100bp*2, paired-end, strand-specific, polyA-positive RNA-seq on hearts from 2 group of adult zebrafish, in which one was sham group and the other 7 days after heart tip amputation (7dpa). We found pathways involving hydrogen peroxidate related functions significantly up-regulated in 7dpa group, indicating its role in heart regeneration.

2014-12-24 | GSE50203 | GEO

Proteomic analysis of extracellular matrix remodeling during zebrafish heart regeneration

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

scRNAseq of post-amputation regenerating zebrafish cardiac ventricle

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

Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair

Project description:The adult mammalian heart heals after myocardial infarction (MI) by deposition of scar tissue, leading to downstream arrhythmia, remodelling and heart failure1. In contrast, adult zebrafish and neonatal mouse hearts are capable of regenerating after injury. Macrophages are key mediators of tissue repair and appear to be required for both regeneration and healing by scar formation, but the mechanisms underlying these distinct roles are poorly understood2-4. Here we investigated how macrophages differentially influence the mode of repair by determining their responses in scar-free versus scar-induced healing, comparing ventricular resection with cryo-injured adult zebrafish hearts and neonatal versus adult mouse hearts after MI. Unbiased transcriptomics revealed molecular programmes implicating macrophages in the initiation and resolution of inflammation to dictate the kinetics of scarring during zebrafish regeneration and the activation of direct and indirect pathways to drive fibrosis in the adult mouse heart. Most notably we observed up-regulation of collagen isoforms in both zebrafish and mouse macrophages following injury. Adoptive transfer of macrophages, from resected zebrafish hearts into cryo-injured hosts and splenic monocyte-derived macrophages from adult mouse donors into neonatal hearts, enhanced scar formation and induced fibrosis, respectively, via cell autonomous production of collagen. In zebrafish, macrophage-specific targeting of collagen 4a binding protein and cognate collagen 4a1 followed by transfer led to significantly reduced scarring in cryo-injured hosts, as further evidence of a direct macrophage contribution to collagen deposition and scar formation. These findings contrast with the current model of scarring, whereby collagen is laid down exclusively by myofibroblasts, and implicate macrophages as critical regulators of heart repair.

2019-12-18 | GSE126772 | GEO

Proteomics analysis of extracellular matrix remodeling during zebrafish heart regeneration

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 heartregeneration has been comparatively rarely explored. Here, we set out to characterize theECM protein composition inadult 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 dayspost-amputation) time-point analyzed. Regeneration associated withsharp increases inspecific ECM proteins, and with an overall decrease in collagens and cytoskeletal proteins. We finally tested by atomic force microscopythat the changes in ECM composition translatedto decreased ECM stiffness. Our cumulative results identify changes in the protein composition and mechanical properties of the zebrafish heart ECM during regeneration.

2019-08-22 | PXD011627 | Pride

Microarray analysis of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposed Amputated Adult Zebrafish Heart Ventricles

Project description:The purpose of this experiment is to understand which transcripts are differentially expressed following exposure to TCDD. We used microarrays to understand global changes in gene signal intensity Adult zebrafish (danio rerio) were injected (i.p) to vehicle control or TCDD (70 ng/g) one day prior to heart ventricle amputation. A subset of fish were exposed but the hearts were not amputated. Amputated hearts were collected at 6 hours post amputation and 7 days post amputation and processed for microarray analysis

2011-11-29 | E-GEOD-33981 | biostudies-arrayexpress

Transcriptome analysis on wild type and mvp mutant zebrafish ventricles at 7dpa by Next Generation Sequencing

Project description:In contrast to mammals, the adult zebrafish hearts can regenerate within a short period. Upregulation of major vault protein (Mvp) expression after ventricle resection. To determine the impact of loss of mvp on transcriptome during heart regeneration, we pursued transcriptome analysis (RNA-Seq) on wild type and mvp mutant zebrafish hearts at 7 day-post-amputation.

2020-09-01 | GSE157170 | GEO

MicroRNA expression profiling of zebrafish heart regeneration

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

Disruption of immune responses hindered cardiac repair in zebrafish

Project description:We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found zebrafish treated with anti-inflammatory steroid, beclomethasone, would suffer significantly reduction of its heart regenerative ability, leading to excessive collagen deposition in wound. Microarray approach was used to evaluate the differential expression of heart transcriptome between normal and impaired healing zebrafish, which provides an overall assessment of significant genes that were important for triggering regeneration in the hemostasis-inflammation phase. Three sets of samples each containing 10 zebrafish hearts were used: sham operation, DMSO-1dpa, beclomethasone-1dpa. (dpa= days post amputation) Objects were pre-exposed to water containing 0.25M-NM-<M beclomethasone or DMSO for 1 day. After ventricular resection surgery, objects were sacrificed with their ventricles harvested at the next day (i.e. 1dpa)

2013-06-24 | E-GEOD-41618 | biostudies-arrayexpress

RNA-seq experiments on heart regeneration in WT, foxm1 and dusp6 mutants.

Project description:The study compares gene expression profile at several stages post amputation of the adult zebrafish ventricular heart between zebrafish mutants and WT siblings. The first experiment was to identify genes that are activated in response to cardiac injury at 3 and 7 days post amputation (dpa). Dusp6 mutant hearts were reported to show an enhanced regenerative response. For this experiment, bulk RNA seq was obtained from WT and Dusp6 mutant hearts and genes increased at 3 and 7 dpa were identified. The forkhead transcription factor, foxm1, showed increased expression in cardiomyocytes and follow up studies show that it is required to regulate cardiomyocyte proliferation. This was further explored with RNA-seq experiments comparing WT and foxm1 mutant hearts at 3dpa. We identified genes normally expressed in proliferating cells to be decreased in the foxm1 mutants.

2022-06-22 | GSE201139 | GEO

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