Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Heart ventricle regeneration in the lizard Eublepharis macularius, the leopard gecko

ABSTRACT: Among mammals, injury to the heart typically results in scar formation and diminished cardiovascular function. In contrast, some teleost fish and salamanders can replace damaged heart tissue and restore overall function. For most species, however, less is known. Here, we investigate cardiac self-repair in an amniote capable of multi-tissue regeneration, the leopard gecko (Eublepharis macularius). To create a heart lesion, we placed a liquid nitrogen-cooled metal probe directly onto the ventricle. The result was a cryoinjury to ~20% of the ventricle. Cardiac cryoinjury induced localized cardiac cell death, followed by an increase in cell proliferation by injury-adjacent cardiomyocytes and non-cardiomyocytes. By 100 days, the histology of the ventricular myocardium was near-completely restored. Echocardiography and invasive hemodynamic monitoring demonstrated that global cardiac function is restored within this timeframe, verifying functional replacement of the myocardium. To explore the molecular basis, we performed bulk RNA sequencing of the injury-adjacent tissue and found that many of the molecular mechanisms common to other cardiac regenerating species, including genes involved in heart development, glycolysis, and extracellular matrix deposition, are also conserved in geckos. Taken together, this work expands the comparative framework of heart regeneration to include reptiles and indicates that the ability to replace missing or damaged cardiomyocytes is shared across more than 350 million years of evolution.

ORGANISM(S): Eublepharis macularius

PROVIDER: GSE326865 | GEO | 2026/05/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Pre-existent adult sox10+ cardiomyocytes contribute to myocardial regeneration in the zebrafish

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

Profiling proliferative cells and their progeny in damaged murine hearts

Project description:The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.

2018-12-04 | GSE102048 | GEO

The ion channel Trpc6a regulates the cardiomyocyte regenerative response to mechanical stretch

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

Identifying downstream targets of ankrd1a in heart regeneration after cryoinjury in adult zebrafish

Project description:In contrast to humans, zebrafish have a remarkable ability to regenerate injured heart through a complex and highly orchestrated process involving all cardiac structures. During regeneration, the major source of new myocardial cells are resident cardiomyocytes, which dedifferentiate and reinitiate proliferation, invading the area of injury to replace the lost myocardium. The response of the myocardium and the coronary vasculature is preceded by activation of epi- and endocardium, which form active scaffolds to provide mechanical and paracrine support to guide regeneration.Zebrafish ankrd1a was found activated in differentiated and proliferating cardiomyocytes restricted to the border zone, as well as in protrusions of cardiomyocytes that invade the scar. The TgBAC(ankrd1a:EGFP) transgene was not detected in epicardial or endocardial cells of regenerating zebrafish heart. Transcriptomic analysis of cryoinjured ventricles showed that lack of functional ankrd1a at 7 dpci leads to change in expression of genes involved in antigen processing and presentation of peptide or polysaccharide antigen via MHC class II, cellular extravasation, cell-cell adhesion and heart valve development.

2025-06-25 | GSE285387 | GEO

Telomerase is essential for zebrafish heart regeneration

Project description:Unlike human hearts, zebrafish hearts efficiently regenerate after injury. Regeneration is driven by the strong proliferation response of its cardiomyocytes to injury. In this study, we show that active telomerase is required for cardiomyocyte proliferation and full organ recovery, supporting the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction. Heart transcriptomes of WT and telomerase defective adult zebrafish animals were profiled by RNASeq, in control conditions and 3 days after heart cryoinjury.

2015-08-06 | E-GEOD-71755 | biostudies-arrayexpress

Single epicardial cell transcriptome sequencing identifies Caveolin-1 as an essential factor in zebrafish heart regeneration

Project description:By contrast with mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of spared cardiomyocytes. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration through paracrine effects and as a multipotent cell source, and has received recent attention as a target in cardiac repair strategies. While it is recognized that epicardium is required for muscle regeneration and itself has high regenerative potential, the extent of cellular heterogeneity within epicardial tissue is largely unexplored. In this study, we performed transcriptome analysis on dozens of epicardial lineage cells purified from zebrafish harboring a transgenic reporter for the pan-epicardial gene tcf21. Hierarchical clustering analysis suggested the presence of at least three epicardial cell subsets defined by expression signatures. We validated many new pan-epicardial and epicardial markers by alternative expression assays. Additionally, we explored the function of the scaffolding protein and main component of caveolae, caveolin-1 (cav1), which was present in each epicardial subset. In BAC transgenic zebrafish, cav1 regulatory sequences drove strong expression in ostensibly all epicardial cells and in coronary vascular endothelial cells. Moreover, cav1 mutant zebrafish generated by genome editing showed grossly normal heart development and adult cardiac anatomy, but displayed profound defects in injury-induced cardiomyocyte proliferation and heart regeneration. Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration. Deep sequencing of isolated single epicardial cells

2015-12-15 | E-GEOD-75583 | biostudies-arrayexpress

A paternal cardiac lesion induces cardiac adaptation in the offspring

Project description:Background: Following cardiac injury, whether the heart is permanently damaged or regenerating, distal organs are subjected to changes in physiological function. It remains largely unknown whether a cardiac lesion can affect gametes and transmit heritable changes to subsequent generations. Here, we report the influence of paternal cardiac injury on the following generation. Methods: We studied the intergenerational influence of neonatal cardiac injury in the mouse. Neonatal male mice were subjected to ventricular cryoinjury, crossed at adulthood, and their sires were compared with litters derived from uninjured male mice. We used echocardiography, histology, and single nuclei RNA-sequencing to thoroughly characterize cardiac morphology, composition, function, and response to cardiac insult. Results: We show that paternal cardiac injury affects the heart morphology of offspring under physiological conditions. Furthermore, in response to the same injury, the F1 generation derived from injured fathers shows better systemic and cardiac recovery, with non-pathological left ventricular enlargement and improved cardiac function. This is accompanied by the activation of the immune system healing program at 3 weeks post-injury, together with enhanced transcription of genes associated with physiological hypertrophy. Conclusions: The memory of a paternal neonatal lesion can be transmitted to offspring and improve their recovery from a cardiac insult.

2024-11-08 | GSE254827 | GEO

Comparison of gene expression in cardiac macrophages from P1 or P14 mice 3 days following MI

Project description:Myocardial infarction (MI) leads to cardiomyocyte death, which triggers an immune response that clears debris and restores tissue integrity. In the adult heart, the immune system facilitates scar formation, which repairs the damaged myocardium but compromises cardiac function. In neonatal mice, the heart can regenerate fully without scarring following MI; however, this regenerative capacity is lost by P7. The signals that govern neonatal heart regeneration are unknown. By comparing the immune response to MI in mice at P1 and P14, we identified differences in the magnitude and kinetics of monocyte and macrophage responses to injury. Using a cell-depletion model, we determined that heart regeneration and neoangiogenesis following MI depends on neonatal macrophages. Neonates depleted of macrophages were unable to regenerate myocardia and formed fibrotic scars, resulting in reduced cardiac function and angiogenesis. Immunophenotyping and gene expression profiling of cardiac macrophages from regenerating and nonregenerating hearts indicated that regenerative macrophages have a unique polarization phenotype and secrete numerous soluble factors that may facilitate the formation of new myocardium. Our findings suggest that macrophages provide necessary signals to drive angiogenesis and regeneration of the neonatal mouse heart. Modulating inflammation may provide a key therapeutic strategy to support heart regeneration. Total RNA was isolated from CD11b+Ly6G- cells sorted from hearts 3 days following ligation of LAD. 6 samples total: Triplicates of cells from P1 mice and from P14 mice

2014-01-31 | E-GEOD-54530 | biostudies-arrayexpress

Single cell profiling of salamander heart under homeostasis and after cryoinjury.

Project description:Heart disease is the leading cause of mortality worldwide due to the limited regenerative capacity of the mammalian heart. Myocardial infarction causes massive cardiomyocyte apoptosis that is replaced by a fibrotic scar. In contrast to mammals, certain vertebrates such as fish and amphibians can regenerate cardiac muscle without scarring. Here, we established a cryoinjury model in the salamander species, Pleurodeles waltl. We performed single-cell RNA sequencing to profile the salamander heart and identified CLDN6 as a specific marker of epicardium, the outermost mesothelial layer enclosing the heart. Notably, lineage tracing experiments showed differentiation of CLDN6+ epicardium-derived cell intermediates into cardiomyocytes in response to injury. Additionally, scRNA-seq experiments suggested a differentiation trajectory that describes epicardial cell to myocyte conversion. Furthermore, ablation of these intermediates with Clostridium perfringens enterotoxin (CPE) blocked cardiac regeneration.

2022-02-21 | GSE180914 | GEO

Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish

Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.

2020-07-13 | PXD016235 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data