An injury responsive enhancer promotes heart regeneration in zebrafish
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE211424 | GEO | 2023/07/24
REPOSITORIES: GEO
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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. RNA-seq: hearts from sham or 7dpa adult zebrafish
2014-12-24 | E-GEOD-50203 | 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: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
Project description:Zebrafish have the remarkable ability to regenerate body parts including the heart, spinal cord and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage-larvae also possess the ability to regenerate the caudal fin. A comparative genomic analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of Retinoic acid (RA), as one of the highly induced genes across the three regeneration platforms. Experiment Overall Design: The caudal fin of zebrafish larvae at 2days post fertilization were amputated. Caudal fin tissue at 2dpf and regenerating fins were isolated at 1, 2and 3 days post amputation. Three replicates were collected at each time point. 150 fins were pooled to comprise one replicate.
2008-04-07 | E-GEOD-10188 | 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 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
Project description:Platelet-derived growth factor (PDGF) signaling regulates perivascular cell or mural cell association with the blood-vessel endothelial cells. Mural cells express the receptor of the signaling, pdgfrb. Besides mural cells the outer epithelial layer of the heart, epicardium and epicardial derived cells express pdgfrb. In this dataset we characterized pdgfrb expressing cells in adult zebrafish heart ventricles in AB wildtype fish, pdgfrb loss-of-function mutant fish. Since pdgfrb is activated in injured zebrafish heart, we aslo compared pdgfrb expressing cells in injured (amputated, 7 days post amputation) heart ventricle with similar cells in uninjured hearts.
2022-02-19 | GSE188511 | GEO
Project description:Background—YAP, the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEAD sequence specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyocyte proliferation and survival. However, the direct transcriptional targets through which YAP exerts its effects are poorly defined. Methods and Results—To identify genes directly regulated by YAP in cardiomyocytes, we combined differential gene expression analysis in YAP gain- and loss-of-function with genome-wide identification of YAP bound loci using chromatin immunoprecipitation and high throughput sequencing. This screen identified Pik3cb, encoding p110β, a catalytic subunit of phosphoinositol-3-kinase (PI3K), as a candidate YAP effector that promotes cardiomyocyte proliferation and survival. We validated YAP and TEAD occupancy of a conserved enhancer within the first intron of Pik3cb, and show that this enhancer drives YAP-dependent reporter gene expression. Yap gain- and loss-of-function studies indicated that YAP is necessary and sufficient to activate the PI3K-Akt pathway. Like Yap, Pik3cb gain-of-function stimulated cardiomyocyte proliferation, and Pik3cb knockdown dampened the YAP mitogenic activity. Reciprocally, Yap loss-of-function impaired heart function and reduced cardiomyocyte proliferation and survival, all of which were significantly rescued by AAV-mediated Pik3cb expression. Conclusion—Pik3cb is a crucial direct target of YAP, through which the YAP activates PI3K-AKT pathway and regulates cardiomyocyte proliferation and survival. Yap wild type ChIPseq and input
2015-02-20 | E-GEOD-57717 | biostudies-arrayexpress
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
Project description:Regulation of organ size is important for development and tissue homeostasis. In Drosophila, Hippo signaling controls organ size by regulating the activity of a TEAD transcription factor, Scalloped, through modulation of its coactivator protein Yki. The role of mammalian Tead proteins in growth regulation, however, remains unknown. Here we examined the role of mouse Tead proteins in growth regulation. In NIH3T3 cells, cell density and Hippo signaling regulated the activity of Tead proteins by modulating nuclear localization of a Yki homologue, Yap, and the resulting change in Tead activity altered cell proliferation. Tead2-VP16 mimicked Yap overexpression, including increased cell proliferation, reduced cell death, promotion of EMT, lack of cell contact inhibition, and promotion of tumor formation. Growth promoting activities of various Yap mutants correlated with their Tead-coactivator activities. Tead2-VP16 and Yap regulated largely overlapping sets of genes. However, only a few of the Tead/Yapregulated genes in NIH3T3 cells were affected in Tead1-/-;Tead2-/- or Yap-/- embryos. Most of the previously identified Yap-regulated genes were not affected in NIH3T3 cells or mutant mice. In embryos, levels of nuclear Yap and Tead1 varied depending on cell types. Strong nuclear accumulation of Yap and Tead1 were seen in myocardium, correlating with requirements of Tead1 for proliferation. However, their distribution did not always correlate with proliferation. Taken together, mammalian Tead proteins regulate cell proliferation and contact inhibition as a transcriptional mediator of Hippo signaling, but the mechanisms by which Tead/Yap regulate cell proliferation differ depending on cell types, and Tead, Yap and Hippo signaling may play multiple roles in mouse embryos. We used microarrays to know the gene expression profiles regurated by Tead2-VP16, Tead2-EnR, Yap, and cell density in NIH3T3 cells. Keywords: Cell density, genetic modification Tead2-VP16-, Tead2-EnR-, Yap- and control vector-expressing cells were cultured at low or high density for RNA extraction and hybridization on Affymetrix microarrays.
2008-11-20 | E-GEOD-12498 | biostudies-arrayexpress
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