Heart morphogenesis and regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA894685 | ENA |
REPOSITORIES: ENA
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Project description:hapln1a+ cells guide coronary growth during heart morphogenesis and regeneration [Dev, hapln1a+ cells]
| PRJNA894591 | ENA
Project description:hapln1a+ cells guide coronary growth during heart morphogenesis and regeneration [Reg, hapln1a+ cell]
| PRJNA894688 | ENA
Project description:hapln1a+ cells guide coronary growth during heart morphogenesis and regeneration [Dev, tcf21+ cells]
| PRJNA894687 | ENA
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:As cardiac regeneration requires new coronary vessels, exploring the underlying mechanisms behind revascularization will facilitate the development of regenerative therapies for heart failure. Although multiple tissues and chemokines likely orchestrate coronary formation, the interaction between coronary growth and guidance cues remains unclear. Here, by applying single-cell RNA-sequencing (scRNA-seq) analysis, we examined gene expression in zebrafish epicardial cells during coronary vascularization and identified hapln1a-expressing epicardial cells enriched with vascular-regulating genes. Fluorescence reporter assays indicated hapln1a+ cells not only envelop coronary vessels, but also form cellular shear structures in ahead of coronary tips. Live imaging analyses demonstrated coronary growth along the pre-formed shears, with depletion of hapln1a+ cells blocking this growth. Further, we found hapln1a+ cells also pre-lead coronary tips in the regenerating area and hapln1a+ cell loss inhibits coronary revascularization. To characterize the molecular nature of hapln1a+ cells during coronary growth, we profiled hapln1a+ cells in juvenile and regenerating hearts and detected expression of the cell adhesion and migration regulator serpine1 in hapln1a+ cells adjacent to coronary tips. Pharmacological inhibition of serpine1 function blocked coronary vascularization and revascularization. Altogether, our studies reveal that hapln1a+ cells are required for coronary production during heart morphogenesis and regeneration, by establishing a microenvironment to facilitate guided coronary growth.
2023-05-26 | GSE216647 | GEO
Project description:As cardiac regeneration requires new coronary vessels, exploring the underlying mechanisms behind revascularization will facilitate the development of regenerative therapies for heart failure. Although multiple tissues and chemokines likely orchestrate coronary formation, the interaction between coronary growth and guidance cues remains unclear. Here, by applying single-cell RNA-sequencing (scRNA-seq) analysis, we examined gene expression in zebrafish epicardial cells during coronary vascularization and identified hapln1a-expressing epicardial cells enriched with vascular-regulating genes. Fluorescence reporter assays indicated hapln1a+ cells not only envelop coronary vessels, but also form cellular shear structures in ahead of coronary tips. Live imaging analyses demonstrated coronary growth along the pre-formed shears, with depletion of hapln1a+ cells blocking this growth. Further, we found hapln1a+ cells also pre-lead coronary tips in the regenerating area and hapln1a+ cell loss inhibits coronary revascularization. To characterize the molecular nature of hapln1a+ cells during coronary growth, we profiled hapln1a+ cells in juvenile and regenerating hearts and detected expression of the cell adhesion and migration regulator serpine1 in hapln1a+ cells adjacent to coronary tips. Pharmacological inhibition of serpine1 function blocked coronary vascularization and revascularization. Altogether, our studies reveal that hapln1a+ cells are required for coronary production during heart morphogenesis and regeneration, by establishing a microenvironment to facilitate guided coronary growth.
2023-05-26 | GSE216646 | GEO
Project description:As cardiac regeneration requires new coronary vessels, exploring the underlying mechanisms behind revascularization will facilitate the development of regenerative therapies for heart failure. Although multiple tissues and chemokines likely orchestrate coronary formation, the interaction between coronary growth and guidance cues remains unclear. Here, by applying single-cell RNA-sequencing (scRNA-seq) analysis, we examined gene expression in zebrafish epicardial cells during coronary vascularization and identified hapln1a-expressing epicardial cells enriched with vascular-regulating genes. Fluorescence reporter assays indicated hapln1a+ cells not only envelop coronary vessels, but also form cellular shear structures in ahead of coronary tips. Live imaging analyses demonstrated coronary growth along the pre-formed shears, with depletion of hapln1a+ cells blocking this growth. Further, we found hapln1a+ cells also pre-lead coronary tips in the regenerating area and hapln1a+ cell loss inhibits coronary revascularization. To characterize the molecular nature of hapln1a+ cells during coronary growth, we profiled hapln1a+ cells in juvenile and regenerating hearts and detected expression of the cell adhesion and migration regulator serpine1 in hapln1a+ cells adjacent to coronary tips. Pharmacological inhibition of serpine1 function blocked coronary vascularization and revascularization. Altogether, our studies reveal that hapln1a+ cells are required for coronary production during heart morphogenesis and regeneration, by establishing a microenvironment to facilitate guided coronary growth.
2023-05-26 | GSE216648 | GEO
Project description:The epicardium, a thin mesothelial tissue layer that encompasses the heart, is a dynamic structure that is essential for cardiac regeneration in species with elevated regenerative capacity like zebrafish. To dissect epicardial cell states and associated pro-regenerative functions, we performed single-cell RNA-sequencing and identified 7 epicardial cell clusters in adult zebrafish, with 3 of these clusters enhanced during regeneration. ECM components encoded by hapln1 paralogs label an enriched epicardial cell type that accumulates and encloses dedifferentiated and proliferating cardiomyocytes during regeneration. Genetic inactivation of hapln1b, or induced genetic depletion of hapln1a-expressing cells, disrupted cardiomyocyte proliferation and heart regeneration. hapln1a+ cells first emerge at the juvenile stage, when they associate with and are required for cardiogenic foci that direct growth of the juvenile heart. Our findings identify a subset of epicardial cells that emerges in post-embryonic animals and sponsors regions of active cardiomyogenesis during heart growth and regeneration
2022-06-17 | GSE172511 | GEO
Project description:hapln1 defines an epicardial cell subpopulation that establishes cardiogenic hotspots during heart morphogenesis and regeneration
| PRJNA723588 | ENA
Project description:Background: The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. To uncover the molecular mechanisms underlying neonatal heart regeneration, we compared the transcriptomes and epigenomes of regenerative and non-regenerative mouse hearts over a 7-day time period following myocardial infarction. Methods: RNA-Seq, H3K27ac ChIP-Seq and H3K27me3 ChIP-Seq were performed on ventricular samples from regenerative P1 or non-regenerative P8 mouse hearts at +1.5d, +3d and +7d after MI or Sham surgery to assemble the transcriptome, active chromatin and repressed chromatin landscapes during neonatal heart regeneration. Dynamic enhancer landscapes from mouse hearts during cardiac development were analyzed using data from ENCODE. Effects on cardiomyocyte proliferation and cardiac function from selected factors identified in this study were tested using BrdU/EdU pulse-labeling or mouse models coupled with immunohistochemistry and echocardiography. Results: By integrating gene expression profiles with histone marks associated with active or repressed chromatin, we identified transcriptional programs underlying neonatal heart regeneration and the blockade to regeneration in later life. Our results reveal a unique immune response in regenerative hearts and an embryonic cardiogenic gene program that remains active during neonatal heart regeneration. Among the unique immune factors and embryonic genes associated with cardiac regeneration, we identified Ccl24, which encodes a cytokine, and Igf2bp3, which encodes an RNA-binding protein, as previously unrecognized regulators of cardiomyocyte proliferation. Conclusions: Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that might be modulated to promote heart regeneration.
2019-07-15 | GSE123867 | GEO