Hypoxia induces myocardial regeneration in zebrafish
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE39842 | GEO | 2013/01/15
SECONDARY ACCESSION(S): PRJNA171838
REPOSITORIES: GEO
Similar Datasets
Project description:Conditional expression of dominant-negative HIF1a in zebrafish cardiomyocytes severely inhibits heart regeneration. To understand more about the mechanism, we performed microarray analysis of wildtype regenerating zebrafish and dnHIF1a regenerating zebrafish to determine which genes are regulated by hypoxia/HIF1a. We amputated both wildtype and dnHIF1a zebrafish and allowed them to regenerate for 7 days, then compared their transcriptomic profile with unamputated wildtype and dnHIF1a zebrafish, respectively.
2013-01-15 | E-GEOD-39842 | biostudies-arrayexpress
Project description:During heart regeneration in the zebrafish, fibrotic tissue is replaced by newly formed cardiomyocytes derived from pre-existing ones. It is unclear whether the heart is comprised of several cardiomyocyte populations bearing different capacity to replace lost myocardium. Here, using sox10 genetic fate mapping, we identified a subset of pre-existent cardiomyocytes in the adult zebrafish heart with a distinct gene expression profile that expanded massively after cryoinjury. Genetic ablation of sox10+ cardiomyocytes severely impaired cardiac regeneration revealing that they play a crucial role for heart regeneration.
2019-09-30 | GSE133571 | GEO
Project description:Heart failure is a leading cause of mortality and morbidity in the developed world, partly because mammals lack the ability to regenerate heart tissue. Whether this is due to evolutionary loss of regenerative mechanisms present in other organisms or to an inability to activate such mechanisms is currently unclear. Here, we decipher mechanisms underlying heart regeneration in adult zebrafish and show that the molecular regulators of this response are conserved in mammals. We identified miR-99/100 and Let-7a/c, and their protein targets smarca5 and fntb, as critical regulators of cardiomyocyte dedifferentiation and heart regeneration in zebrafish. Although human and murine adult cardiomyocytes fail to elicit an endogenous regenerative response following myocardial infarction, we show that in vivo manipulation of this molecular machinery in mice results in cardiomyocyte dedifferentiation and improved heart functionality after injury. These data provide a proof-of-concept for identifying and activating conserved molecular programs to regenerate the damaged heart. Analysis of miRNA levels in regenerating zebrafish hearts
2014-11-20 | E-GEOD-62386 | biostudies-arrayexpress
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:The underlying cause of systolic heart failure is the inability of the adult mammalian heart to regenerate damaged myocardium. In contrast, some vertebrate species and immature mammals are capable of full cardiac regeneration following multiple types of injury through cardiomyocyte proliferation. Little is known about what distinguishes proliferative cardiomyocytes from terminally differentiated, nonproliferative cardiomyocytes. Recently, several reports have suggested that oxygen metabolism and oxidative stress play a pivotal role in regulating the proliferative capacity of mammalian cardiomyocytes. Moreover, reducing oxygen metabolism in the adult mammalian heart can induce cardiomyocyte cell cycle reentry through blunting oxidative damage, which is sufficient for functional improvement following myocardial infarction. Here we concisely summarize recent findings that highlight the role of oxygen metabolism and oxidative stress in cardiomyocyte cell cycle regulation, and discuss future therapeutic approaches targeting oxidative metabolism to induce cardiac regeneration.
| S-EPMC6157643 | biostudies-other
Project description:Cardiac regeneration occurs primarily through proliferation of existing cardiomyocytes, yet the regenerative response also involves complex interactions between distinct cardiac cell types including not only cardiomyocytes, but also non-cardiomyocytes (nonCMs). However, the molecular features and cellular functions of the highly heterogeneous populations of nonCMs and how these populations cooperate to regenerate the injured heart remain largely unexplored. Using the newly developed LIGER algorithm that allows flexible modeling across highly diverse single-cell datasets, we analyzed the transcriptome dynamics of 61,977 individual nonCMs isolated at multiple time points during zebrafish heart regeneration. Combining single-cell analysis and in situ hybridization, we identified major nonCM cell types, including multiple novel subpopulations with unique tempo-spatial distributions and highly cooperative interactions in the regenerating heart. Interestingly, genetic perturbation of macrophage function by kit knockout led to accumulation of fibrotic deposits and severely compromised cardiomyocyte proliferation and myocardium regeneration. Our single-cell transcriptomic analysis of nonCMs during cardiac regeneration provides a blueprint for interrogating the molecular and cellular basis of cardiac regeneration.
2021-09-06 | GSE145980 | GEO
Project description:Cardiac regeneration occurs primarily through proliferation of existing cardiomyocytes, yet the regenerative response also involves complex interactions between distinct cardiac cell types including not only cardiomyocytes, but also non-cardiomyocytes (nonCMs). However, the molecular features and cellular functions of the highly heterogeneous populations of nonCMs and how these populations cooperate to regenerate the injured heart remain largely unexplored. Using the newly developed LIGER algorithm that allows flexible modeling across highly diverse single-cell datasets, we analyzed the transcriptome dynamics of 61,977 individual nonCMs isolated at multiple time points during zebrafish heart regeneration. Combining single-cell analysis and in situ hybridization, we identified major nonCM cell types, including multiple novel subpopulations with unique tempo-spatial distributions and highly cooperative interactions in the regenerating heart. Interestingly, genetic perturbation of macrophage function by kit knockout led to accumulation of fibrotic deposits and severely compromised cardiomyocyte proliferation and myocardium regeneration. Our single-cell transcriptomic analysis of nonCMs during cardiac regeneration provides a blueprint for interrogating the molecular and cellular basis of cardiac regeneration.
2021-09-06 | GSE145979 | 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:We compared transcriptional profiles of regenerating zebrafish caudal fins following fin amputation with profiles from uninjured zebrafish caudal fins
2016-04-08 | GSE76564 | GEO
Project description:We compared transcriptional and chromatin profiles of regenerating zebrafish hearts following genetic ablation with profiles from uninjured zebrafish hearts.
2016-04-08 | GSE75894 | GEO