Early regenerative capacity in the porcine heart
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ABSTRACT:
PROVIDER: PRJNA475704 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7294220_1.fastq.gz | Fastqsanger.gz | |||
| SRR7294220_2.fastq.gz | Fastqsanger.gz | |||
| SRR7294230_1.fastq.gz | Fastqsanger.gz | |||
| SRR7294230_2.fastq.gz | Fastqsanger.gz | |||
| SRR7294240_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: The adult mammalian heart has limited ability to repair itself following injury. Zebrafish, newts and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. It is unknown if hearts of young large mammals can regenerate. Methods: We examined the regenerative capacity of the pig heart in neonatal animals (ages: 2, 3 or 14 days postnatal) after myocardial infarction (MI) or sham procedure. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance (CMR) imaging and echocardiography. Bromodeoxyuridine pulse-chase labeling, histology, immunohistochemistry and Western blotting were performed to study cell proliferation, sarcomere dynamics and cytokinesis and to quantify myocardial fibrosis. RNA-sequencing was also performed. Results: After MI, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day old pigs. In contrast, older animals developed full-thickness myocardial scarring, thinned walls and did not recover function. Genome wide analyses of the infarct zone revealed a strong transcriptional signature of fibrosis in 14-day old animals that was absent in 2-day old pigs, which instead had enrichment for cytokinesis genes. In regenerating hearts of the younger animals, up to 10% of CMs in the border zone of the MI showed evidence of DNA replication that was associated with markers of myocyte division and sarcomere disassembly. Conclusions: Hearts of large mammals have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth.
2018-09-12 | GSE115665 | GEO
Project description:Previous studies have suggested that the heart may be capable of limited repair and regeneration in response to a focal injury while other studies indicate that the mammalian heart has no regenerative capacity. To further explore this issue, we performed a series of superficial and transmural myocardial injuries in C57BL/6 and MRL/MpJ adult mice. At defined time intervals following the respective injury (Days 3, 14, 30 and 60) we examined cardiac function using echocardiography, morphology, FACS cell sorting for BrdU positive cells and molecular signature using microarray analysis. We observed complete restoration of myocardial function in the superficial MRL cryoinjured heart and significantly less scar formation as compared to the injured hearts of C57BL/6 mice. Following a severe transmural myocardial injury, the MRL mouse has increased survival and decreased ventricular remodeling compared to the C57BL/6 mouse but without evidence of significant regeneration. The cytoprotective program observed in the severely injured MRL heart is in part due to increased vasculogenesis and decreased apoptosis that limits the extension of the injury. We conclude that C57BL/6 and MRL injured hearts have evidence of limited myocardial regeneration, in response to superficial injury, but the improved function and survival observed in the MRL mouse heart following severe injury is not due to significant regenerative processes. Mouse hearts from C57BL/6 and MRL/MpJ strains were injured with LAD ligation and harvested at 3, 30 and 60 days after treatement.
2007-11-23 | E-GEOD-4710 | biostudies-arrayexpress
Project description:Cis-Regulatory Accessibility Directs Muller Glial Development and Regenerative Capacity
| PRJNA565157 | ENA
Project description:The adult zebrafish heart has high regenerative capacity. Heart injury triggers a cascade of events including inflammation, fibrosis, revascularization, and proliferation of cardiomyocytes, culminating in full functional recovery of the heart. However, the first events that are induced upon injury and trigger the regenerative cascade remain elusive. Here, we established in vivo single-cell RNA metabolic labeling in the adult heart to systematically identify the cells that first respond to injury, as well as the processes that are induced in these sentinel cells. We found that activation of damage response pathways including Toll-like receptor signaling and expression of pro-inflammatory genes in macrophages are the first response to heart injury. In conjunction with detailed dissection of single-cell transcriptomics atlases, this finding led us to postulate that macrophage-specific inhibition of Toll-like receptor signaling would improve hallmarks of regeneration, a hypothesis we validated in functional experiments. In summary, our work establishes RNA metabolic labeling as a powerful approach for measuring perturbation response in vivo, identifies macrophages as the sentinel cells of the heart, and highlights the importance of fine-tuning the early pro-inflammatory phase for optimal regenerative outcomes.
2026-03-30 | GSE305090 | GEO
Project description:The adult zebrafish heart has high regenerative capacity. Heart injury triggers a cascade of events including inflammation, fibrosis, revascularization, and proliferation of cardiomyocytes, culminating in full functional recovery of the heart. However, the first events that are induced upon injury and trigger the regenerative cascade remain elusive. Here, we established in vivo single-cell RNA metabolic labeling in the adult heart to systematically identify the cells that first respond to injury, as well as the processes that are induced in these sentinel cells. We found that activation of damage response pathways including Toll-like receptor signaling and expression of pro-inflammatory genes in macrophages are the first response to heart injury. In conjunction with detailed dissection of single-cell transcriptomics atlases, this finding led us to postulate that macrophage-specific inhibition of Toll-like receptor signaling would improve hallmarks of regeneration, a hypothesis we validated in functional experiments. In summary, our work establishes RNA metabolic labeling as a powerful approach for measuring perturbation response in vivo, identifies macrophages as the sentinel cells of the heart, and highlights the importance of fine-tuning the early pro-inflammatory phase for optimal regenerative outcomes.
2026-03-30 | GSE305095 | GEO
Project description:The adult zebrafish heart has high regenerative capacity. Heart injury triggers a cascade of events including inflammation, fibrosis, revascularization, and proliferation of cardiomyocytes, culminating in full functional recovery of the heart. However, the first events that are induced upon injury and trigger the regenerative cascade remain elusive. Here, we established in vivo single-cell RNA metabolic labeling in the adult heart to systematically identify the cells that first respond to injury, as well as the processes that are induced in these sentinel cells. We found that activation of damage response pathways including Toll-like receptor signaling and expression of pro-inflammatory genes in macrophages are the first response to heart injury. In conjunction with detailed dissection of single-cell transcriptomics atlases, this finding led us to postulate that macrophage-specific inhibition of Toll-like receptor signaling would improve hallmarks of regeneration, a hypothesis we validated in functional experiments. In summary, our work establishes RNA metabolic labeling as a powerful approach for measuring perturbation response in vivo, identifies macrophages as the sentinel cells of the heart, and highlights the importance of fine-tuning the early pro-inflammatory phase for optimal regenerative outcomes.
2026-03-30 | GSE305094 | GEO
Project description:miR-375 Regulates Intestinal Crypt Cell Landscape, Proliferation, and Regenerative Capacity
| PRJNA634565 | 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:Zebrafish heart regeneration is a complex process consisting of tempo-spatial coordination of cardiomyocyte (CM) and endothelial cell (EC) regeneration, fibrosis and inflammation. While myocardial, endocardial, and epicardial signaling have been reported to modulate this process, little is known about how leukocyte especially platelet signaling is involved in this regenerative process. Here we report that cloche/npas4l (neuronal PAS domain protein 4 like) is a pro-regenerative platelet factor for adult zebrafish heart regeneration. We found that injury triggered npas4l expression as early as 1 h post ventricular amputation, and haploinsufficiency of npas4l disrupted CM and EC proliferation and heart regeneration in clofv087b/+ and clom39/+ mutants after ventricular resection or nitroreductase (NTR)-mediated CM ablation. By constructing a single-cell transcriptomic atlas, we discovered that npas4l was dynamically expressed in platelets in response to heart injury with robust platelet-CM or -EC interactions via ligand-receptor activity analysis. Decreasing platelets in NTR-mediated depletion or mpl mutants impaired CM and EC proliferation, and over-expression of npas4l in platelets sufficiently made uninjured and injured CM reentry into the cell-cycle and rescued CM and EC proliferation in clofv087b/+ mutants. Furthermore, Npas4l positively regulated Bmp6 expression in platelets and either BMP6 inhibitors or siRNAs decreased CM proliferation and heart regeneration. This work demonstrates, for the first time, that injury-induced platelets are essential for zebrafish heart regeneration and Npas4l is a core platelet transcription factor for fine-tuning heart regeneration partially via Bmp6 signaling.
2025-04-22 | GSE275789 | GEO
Project description:Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA-sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and Agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, Agrin-induced senescence and repair require Egr1, activated by the integrin/FAK-ERK/Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype (SASP) components that promote ECM degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process.
2024-05-07 | GSE253383 | GEO