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Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion
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 n...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558647/ https://www.ncbi.nlm.nih.gov/pubmed/26267307 http://dx.doi.org/10.7554/eLife.07455 |
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author | Yahalom-Ronen, Yfat Rajchman, Dana Sarig, Rachel Geiger, Benjamin Tzahor, Eldad |
author_facet | Yahalom-Ronen, Yfat Rajchman, Dana Sarig, Rachel Geiger, Benjamin Tzahor, Eldad |
author_sort | Yahalom-Ronen, Yfat |
collection | PubMed |
description | 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 a 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. DOI: http://dx.doi.org/10.7554/eLife.07455.001 |
format | Online Article Text |
id | pubmed-4558647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45586472015-09-08 Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion Yahalom-Ronen, Yfat Rajchman, Dana Sarig, Rachel Geiger, Benjamin Tzahor, Eldad eLife Cell Biology 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 a 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. DOI: http://dx.doi.org/10.7554/eLife.07455.001 eLife Sciences Publications, Ltd 2015-08-12 /pmc/articles/PMC4558647/ /pubmed/26267307 http://dx.doi.org/10.7554/eLife.07455 Text en © 2015, Yahalom-Ronen et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Yahalom-Ronen, Yfat Rajchman, Dana Sarig, Rachel Geiger, Benjamin Tzahor, Eldad Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion |
title | Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion |
title_full | Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion |
title_fullStr | Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion |
title_full_unstemmed | Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion |
title_short | Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion |
title_sort | reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558647/ https://www.ncbi.nlm.nih.gov/pubmed/26267307 http://dx.doi.org/10.7554/eLife.07455 |
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