PUBLICATION

Multiple cryoinjuries modulate the efficiency of zebrafish heart regeneration

Authors
Bise, T., Sallin, P., Pfefferli, C., Ja?wi?ska, A.
ID
ZDB-PUB-200716-4
Date
2020
Source
Scientific Reports   10: 11551 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Regeneration*
  • Cell Proliferation
  • Myocytes, Cardiac/cytology
  • Freezing*
  • Microscopy, Fluorescence
  • Zebrafish/physiology*
  • Cell Differentiation
  • Fibrosis
  • Heart/physiology*
  • Cell Lineage
  • Wound Healing
  • Animals, Genetically Modified
  • Image Processing, Computer-Assisted
  • Myocardium/metabolism
  • Phenotype
  • Heart Ventricles/physiopathology
  • Neutrophils/metabolism
  • Transgenes
(all 19)
PubMed
32665622 Full text @ Sci. Rep.
Abstract
Zebrafish can regenerate their damaged hearts throughout their lifespan. It is, however, unknown, whether regeneration remains effective when challenged with successive cycles of cardiac damage in the same animals. Here, we assessed ventricular restoration after two, three and six cryoinjuries interspaced by recovery periods. Using transgenic cell-lineage tracing analysis, we demonstrated that the second cryoinjury damages the regenerated area from the preceding injury, validating the experimental approach. We identified that after multiple cryoinjuries, all hearts regrow a thickened myocardium, similarly to hearts after one cryoinjury. However, the efficiency of scar resorption decreased with the number of repeated cryoinjuries. After six cryoinjuries, all examined hearts failed to completely resolve the fibrotic tissue, demonstrating reduced myocardial restoration. This phenotype was associated with enhanced recruitment of neutrophils and decreased cardiomyocyte proliferation and dedifferentiation at the early regenerative phase. Furthermore, we found that each repeated cryoinjury increased the accumulation of collagen at the injury site. Our analysis demonstrates that the cardiac regenerative program can be successfully activated many times, despite a persisting scar in the wounded area. This finding provides a new perspective for regenerative therapies, aiming in stimulation of organ regeneration in the presence of fibrotic tissue in mammalian models and humans.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    fri2TgTransgenic Insertion
      s928TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        No data available
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-mcm5polyclonalRabbit
        Ab1-N2.261monoclonal
          		IgG1Mouse
          Ab2-col12a1polyclonalGuinea pig
          Ab2-lcp1polyclonalRabbit
          Ab5-mpxpolyclonalIgGRabbit
          1 - 5 of 5
          Show
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          CreEFGCre
          DsRedEFGDsRed
          DsRed2EFGDsRed2
          EGFPEFGEGFP
          1 - 4 of 4
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          Mapping
          No data available
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          Citation
          Bise, T., Sallin, P., Pfefferli, C., Ja?wi?ska, A. (2020) Multiple cryoinjuries modulate the efficiency of zebrafish heart regeneration. Scientific Reports. 10:11551.