Unravelling Zebrafish Heart Regeneration at Single-Cell Level
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE179908 | GEO | 2026/09/01
REPOSITORIES: GEO
Similar Datasets
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: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: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:Myocardial damage caused for example by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In adult mammals, these changes trigger an adaptive cardiomyocyte hypertrophic response which, if the damage is extensive, will ultimately lead to pathological hypertrophy and heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in the adult zebrafish heart and neonatal mice proliferate and completely regenerate the damaged myocardium. We therefore hypothesized that in adult zebrafish, changes in mechanical loading due to myocardial damage may act as a trigger to induce cardiac regeneration. Based, on this notion we sought to identify mechanosensors which could be involved in detecting changes in mechanical loading and triggering regeneration. Here we show using a combination of knockout animals, RNAseq and in vitro assays that the mechanosensitive ion channel Trpc6a is required by cardiomyocytes for successful cardiac regeneration in adult zebrafish. Furthermore, using a cyclic cell stretch assay, we have determined that Trpc6a induces the expression of components of the AP1 transcription complex in response to mechanical stretch. Our data highlights how changes in mechanical forces due to myocardial damage can be detected by mechanosensors which in turn can trigger cardiac regeneration.
2023-12-20 | E-MTAB-13603 | biostudies-arrayexpress
Project description:Cardiac regeneration involves interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been under intense study. Here we report single nuclear RNA sequencing profile of the injured zebrafish heart and identified distinct cardiomyocyte populations in the injured heart. These cardiomyocyte populations indicate diverse functions that includes stress-response, myofibril assembly, proliferation and contraction. The contracting cardiomyocyte population also involves activation of maturation pathways as an early response to injury. This intriguing finding suggests that constant maintenance of distinctive terminally differentiated cardiomyocyte population is important for cardiac function during regeneration. To test this, we determined that cited4a, a p300/CBP transcriptional co-activator, is induced after injury in mature cardiomyocyte population. Moreover, loss-of-cited4a mutants showed increased dedifferentiation, proliferation and accelerated heart regeneration. Thus, suppressing cardiomyocyte maturation pathway activity in injured hearts could be an approach to promote heart regeneration.
2025-01-31 | GSE279845 | GEO
Project description:Cardiac regeneration involves interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been under intense study. Here we report single nuclear RNA sequencing profile of the injured zebrafish heart and identified distinct cardiomyocyte populations in the injured heart. These cardiomyocyte populations indicate diverse functions that includes stress-response, myofibril assembly, proliferation and contraction. The contracting cardiomyocyte population also involves activation of maturation pathways as an early response to injury. This intriguing finding suggests that constant maintenance of distinctive terminally differentiated cardiomyocyte population is important for cardiac function during regeneration. To test this, we determined that cited4a, a p300/CBP transcriptional co-activator, is induced after injury in mature cardiomyocyte population. Moreover, loss-of-cited4a mutants showed increased dedifferentiation, proliferation and accelerated heart regeneration. Thus, suppressing cardiomyocyte maturation pathway activity in injured hearts could be an approach to promote heart regeneration.
2025-01-31 | GSE279843 | 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:Gene regulatory mechanisms that underlie tissue regeneration have been largely studied at the level of transcription. Here, proximity labeling methods identified enhanced presence of Processing body (P-body) marker, Ddx61, in zebrafish heart muscle cells induced to divide by injury or mitogenic stimulation. We found that Ddx61-containing condensates emerge and develop complex, transient structures in cardiomyocytes during cardiogenic settings in adult zebrafish, developing mice, and human stem cell-derived myocardium. Mutations in zebrafish ddx61 disrupted cardiomyocyte cycling and differentiation after cardiac injury or mitogen presence, and DDX61 knockdown in human cardiomyocytes inhibited similar parameters under maturation conditions in vitro. RNA affinity and proteomic profiling implicated mRNAs preferentially associating with Ddx61 during regeneration, and induced transgenic expression of one of these mRNAs, encoding the BMP signaling inhibitor, Chordin, disrupted indicators of heart regeneration after cardiac injury. Our experiments provide evidence that mRNA sorting by specialized context-dependent condensates can modulate gene expression and impact tissue regenerative capacity.
2025-08-26 | GSE246577 | GEO
Project description:The regulatory element, called careg, labels the primordial cardiac wall of the zebrafish heart throughout development and this reporter is transiently activated during regeneration in dedifferentiated cardiomyocytes (CMs) located in the peri-injury zone of the ventricle during heart regeneration. We showed that careg-positive peri-injured CMs are regeneration-competent cells contributing to the formation of the new myocardium. In addition, the careg-positive peri-injured CMs integrate with the fibrotic tissue in the post-infarcted area and are responsive to the TGFβ signaling pathway. To identify the molecular regenerative program of dedifferentiated myocardium, we performed gene expression profiling of careg-positive cardiomyocytes using RNA-sequencing. For this, we isolated four distinct cardiac tissues based on the transgenic fluorescent reporter expression: careg:GFP-negative trabecular mycardium of uninjured ventricle, careg:GFP-positive primordial cardiomyocytes of uninjured heart, careg:GFP-positive peri-injured myocardium of regenerating ventricle at 7dpci and careg:GFP-positive peri-injured myocardium of heart treated with the TGF-β inhibitor, SB431542, at 7dpci.
2026-09-01 | GSE213918 | GEO