PUBLICATION

Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration

Authors
Koth, J., Wang, X., Killen, A.C., Stockdale, W.T., Potts, H.G., Jefferson, A., Bonkhofer, F., Riley, P.R., Patient, R.K., Göttgens, B., Mommersteeg, M.T.M.
ID
ZDB-PUB-200429-4
Date
2020
Source
Development (Cambridge, England)   147(8): (Journal)
Registered Authors
Koth, Jana, Patient, Roger K.
Keywords
Heart, Regeneration, Runx1, ScRNA-seq, Zebrafish
Datasets
GEO:GSE138181
MeSH Terms
  • Annexin A2/metabolism
  • Cicatrix/pathology*
  • Zebrafish/physiology*
  • Cell Proliferation
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Myocardium/pathology*
  • Up-Regulation/genetics
  • Myosin Heavy Chains/metabolism
  • Heart/physiopathology*
  • Mutation/genetics
  • Core Binding Factor Alpha 2 Subunit/genetics
  • Core Binding Factor Alpha 2 Subunit/metabolism*
  • Gene Expression Regulation, Developmental
  • Endocardium/pathology
  • Myofibroblasts/metabolism
  • Myofibroblasts/pathology
  • Animals
  • Muscle, Smooth/metabolism
  • Regeneration*
(all 20)
PubMed
32341028 Full text @ Development
Abstract
Runx1 is a transcription factor that plays a key role in determining the proliferative and differential state of multiple cell types, during both development and adulthood. Here, we report how Runx1 is specifically upregulated at the injury site during zebrafish heart regeneration, and that absence of runx1 results in increased myocardial survival and proliferation, and overall heart regeneration, accompanied by decreased fibrosis. Using single cell sequencing, we found that the wild-type injury site consists of Runx1-positive endocardial cells and thrombocytes that induce expression of smooth muscle and collagen genes. Both these populations cannot be identified in runx1 mutant wounds that contain less collagen and fibrin. The reduction in fibrin in the mutant is further explained by reduced myofibroblast formation and upregulation of components of the fibrin degradation pathway, including plasminogen receptor annexin 2A as well as downregulation of plasminogen activator inhibitor serpine1 in myocardium and endocardium, resulting in increased levels of plasminogen. Our findings suggest that Runx1 controls the regenerative response of multiple cardiac cell types and that targeting Runx1 is a novel therapeutic strategy for inducing endogenous heart repair.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
ox1Tg; s896Tgcold damage: cardiac ventricleAdult
ox1Tg; s896Tgcold damage: cardiac ventricleAdult
runx1hg1/hg1standard conditionsAdult
runx1hg1/hg1standard conditionsAdult
runx1hg1/hg1standard conditionsAdult
runx1hg1/hg1standard conditionsAdult
runx1hg1/hg1cold damage: cardiac ventricleAdult
runx1hg1/hg1cold damage: cardiac ventricleAdult
runx1hg1/hg1cold damage: cardiac ventricleAdult
runx1hg1/hg1cold damage: cardiac ventricleAdult
1 - 10 of 22
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hg1
    		Point Mutation
    ox1TgTransgenic Insertion
      s896TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        Fish
        ox1Tg
        ox1Tg; s896Tg
        runx1hg1/hg1
        runx1hg1/hg1; ox1Tg
        runx1hg1/hg1; ox1Tg; s896Tg
        WT
        1 - 6 of 6
        Show
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        CitrineEFGCitrine
        mCherryEFGmCherry
        1 - 2 of 2
        Show
        Mapping
        No data available
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        Citation
        Koth, J., Wang, X., Killen, A.C., Stockdale, W.T., Potts, H.G., Jefferson, A., Bonkhofer, F., Riley, P.R., Patient, R.K., Göttgens, B., Mommersteeg, M.T.M. (2020) Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration. Development (Cambridge, England). 147(8).