Article | Published:

c-kit+ cells minimally contribute cardiomyocytes to the heart

Nature volume 509, pages 337341 (15 May 2014) | Download Citation

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Abstract

If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit+ cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit+ cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit+ cells amply generated cardiac endothelial cells. Thus, endogenous c-kit+ cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.

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Acknowledgements

This work was supported by grants from the National Institutes of Health (to J.H.v.B., E.M. and J.D.M.). J.D.M. is an investigator of the Howard Hughes Medical Institute.

Author information

Author notes

    • Jop H. van Berlo
    •  & Onur Kanisicak

    These authors contributed equally to this work.

Affiliations

  1. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA

    • Jop H. van Berlo
    • , Onur Kanisicak
    • , Marjorie Maillet
    • , Ronald J. Vagnozzi
    • , Jason Karch
    • , Suh-Chin J. Lin
    •  & Jeffery D. Molkentin
  2. Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA

    • Jop H. van Berlo
  3. Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA

    • Ryan C. Middleton
    •  & Eduardo Marbán
  4. Howard Hughes Medical Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA

    • Jeffery D. Molkentin

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Contributions

J.D.M., J.H.v.B., O.K., M.M., S.-C.J.L. and R.J.V. designed the experiments. S.-C.J.L. designed the Kit allele targeting construct and targeted mice. J.H.v.B. and O.K. designed the breeding, performed histological experiments and animal procedures. R.J.V. performed the qPCR assays. M.M. performed immunohistochemistry. J.K. performed cell culture experiments. E.M. and R.C.M. designed and conducted the independent verification immunohistochemistry with blinded samples. J.D.M. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jeffery D. Molkentin.

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DOI

https://doi.org/10.1038/nature13309

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