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Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion

  1. Yfat Yahalom-Ronen
  2. Dana Rajchman
  3. Rachel Sarig
  4. Benjamin Geiger
  5. Eldad Tzahor  Is a corresponding author
  1. Weizmann Institute of Science, Israel
Research Article
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Cite this article as: eLife 2015;4:e07455 doi: 10.7554/eLife.07455

Abstract

Cardiomyocyte (CM) maturation in mammals is accompanied by a sharp decline in their proliferative and regenerative potential shortly after birth. In this study, we explored the role of the mechanical properties of the underlying matrix in the regulation of CM maturation. We show that rat and mouse neonatal CMs cultured on rigid surfaces exhibited increased myofibrillar organization, spread morphology, and reduced cell cycle activity. In contrast, compliant elastic matrices induced features of CM dedifferentiation, including disorganized sarcomere network, rounding, and conspicuous cell-cycle re-entry. The rigid matrix facilitated nuclear division (karyokinesis) leading to binucleation, while compliant matrices promoted CM mitotic rounding and cell division (cytokinesis), associated with loss of differentiation markers. Moreover, the compliant matrix potentiated clonal expansion of CMs that involves multiple cell divisions. Thus, the compliant microenvironment facilitates CM dedifferentiation and proliferation via its effect on the organization of the myoskeleton. Our findings may be exploited to design new cardiac regenerative approaches.

Article and author information

Author details

  1. Yfat Yahalom-Ronen

    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Dana Rajchman

    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Rachel Sarig

    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Benjamin Geiger

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Eldad Tzahor

    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    eldad.tzahor@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: The experiments were approved by the Animal Care and Use Committee of the Weizmann Institute of Science.

Reviewing Editor

  1. Deepak Srivastava, Gladstone Institute of Cardiovascular Disease, United States

Publication history

  1. Received: March 16, 2015
  2. Accepted: August 11, 2015
  3. Accepted Manuscript published: August 12, 2015 (version 1)
  4. Version of Record published: September 3, 2015 (version 2)

Copyright

© 2015, Yahalom-Ronen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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