PUBLICATION

Myoglobin modulates the Hippo pathway to promote cardiomyocyte differentiation

Authors
Rao, K., Rochon, E., Singh, A., Jagannathan, R., Peng, Z., Mansoor, H., Wang, B., Moulik, M., Zhang, M., Saraf, A., Corti, P., Shiva, S.
ID
ZDB-PUB-240228-13
Date
2024
Source
iScience   27: 109146109146 (Journal)
Registered Authors
Keywords
Biochemistry, Biological sciences, Cell biology, Natural sciences, Specialized functions of cells
MeSH Terms
none
PubMed
38414852 Full text @ iScience
Abstract
The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation. Mechanistically, the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, resulting in phosphorylation and inactivation of yes-associated protein (YAP). In vivo, myoglobin-deficient zebrafish hearts show YAP dephosphorylation and accelerated cardiac regeneration after apical injury. Similarly, myoglobin knockdown in neonatal murine hearts shows increased YAP dephosphorylation and cardiomyocyte cycling. These data demonstrate a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation and highlight myoglobin as a potential target to enhance cardiac development and improve cardiac repair and regeneration.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
mbmbzf4156/zf4156standard conditionsAdultNot DetectedWB
1 - 1 of 1
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Phenotype
Fish Conditions Stage Phenotype Figure
mbzf4156/zf4156standard conditionsAdult
mbzf4156/zf4156standard conditionsAdult
mbzf4156/zf4156standard conditionsAdult
mbzf4156/zf4156standard conditionsAdult
1 - 4 of 4
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf4156
    		Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    mbCRISPR22-mbmbCRISPR
    1 - 1 of 1
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    Fish
    Fish
    mbzf4156/zf4156
    WT
    1 - 2 of 2
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    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab1-mef2polyclonal
      		IgGRabbit
      Ab1-N2.261monoclonal
        		IgG1Mouse
        Ab2-pcnamonoclonalIgG2aMouse
        1 - 3 of 3
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        Orthology
        No data available
        Engineered Foreign Genes
        No data available
        Mapping
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        Citation
        Rao, K., Rochon, E., Singh, A., Jagannathan, R., Peng, Z., Mansoor, H., Wang, B., Moulik, M., Zhang, M., Saraf, A., Corti, P., Shiva, S. (2024) Myoglobin modulates the Hippo pathway to promote cardiomyocyte differentiation. iScience. 27:109146109146.