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Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming

Lower vertebrate and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through the reprogramming of pre-existing cardiomyocytes. However, how cardiac injury initiates signaling pathways controlling this regenerative reprogramming remains to be defined. Here, we utilize in vivo...

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Autores principales: Gálvez-Santisteban, Manuel, Chen, Danni, Zhang, Ruilin, Serrano, Ricardo, Nguyen, Cathleen, Zhao, Long, Nerb, Laura, Masutani, Evan M, Vermot, Julien, Burns, Charles Geoffrey, Burns, Caroline E, del Álamo, Juan C, Chi, Neil C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592682/
https://www.ncbi.nlm.nih.gov/pubmed/31237233
http://dx.doi.org/10.7554/eLife.44816
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author Gálvez-Santisteban, Manuel
Chen, Danni
Zhang, Ruilin
Serrano, Ricardo
Nguyen, Cathleen
Zhao, Long
Nerb, Laura
Masutani, Evan M
Vermot, Julien
Burns, Charles Geoffrey
Burns, Caroline E
del Álamo, Juan C
Chi, Neil C
author_facet Gálvez-Santisteban, Manuel
Chen, Danni
Zhang, Ruilin
Serrano, Ricardo
Nguyen, Cathleen
Zhao, Long
Nerb, Laura
Masutani, Evan M
Vermot, Julien
Burns, Charles Geoffrey
Burns, Caroline E
del Álamo, Juan C
Chi, Neil C
author_sort Gálvez-Santisteban, Manuel
collection PubMed
description Lower vertebrate and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through the reprogramming of pre-existing cardiomyocytes. However, how cardiac injury initiates signaling pathways controlling this regenerative reprogramming remains to be defined. Here, we utilize in vivo biophysical and genetic fate mapping zebrafish studies to reveal that altered hemodynamic forces due to cardiac injury activate a sequential endocardial-myocardial signaling cascade to direct cardiomyocyte reprogramming and heart regeneration. Specifically, these altered forces are sensed by the endocardium through the mechanosensitive channel Trpv4 to control Klf2a transcription factor expression. Consequently, Klf2a then activates endocardial Notch signaling which results in the non-cell autonomous initiation of myocardial Erbb2 and BMP signaling to promote cardiomyocyte reprogramming and heart regeneration. Overall, these findings not only reveal how the heart senses and adaptively responds to environmental changes due to cardiac injury, but also provide insight into how flow-mediated mechanisms may regulate cardiomyocyte reprogramming and heart regeneration.
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spelling pubmed-65926822019-06-26 Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming Gálvez-Santisteban, Manuel Chen, Danni Zhang, Ruilin Serrano, Ricardo Nguyen, Cathleen Zhao, Long Nerb, Laura Masutani, Evan M Vermot, Julien Burns, Charles Geoffrey Burns, Caroline E del Álamo, Juan C Chi, Neil C eLife Developmental Biology Lower vertebrate and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through the reprogramming of pre-existing cardiomyocytes. However, how cardiac injury initiates signaling pathways controlling this regenerative reprogramming remains to be defined. Here, we utilize in vivo biophysical and genetic fate mapping zebrafish studies to reveal that altered hemodynamic forces due to cardiac injury activate a sequential endocardial-myocardial signaling cascade to direct cardiomyocyte reprogramming and heart regeneration. Specifically, these altered forces are sensed by the endocardium through the mechanosensitive channel Trpv4 to control Klf2a transcription factor expression. Consequently, Klf2a then activates endocardial Notch signaling which results in the non-cell autonomous initiation of myocardial Erbb2 and BMP signaling to promote cardiomyocyte reprogramming and heart regeneration. Overall, these findings not only reveal how the heart senses and adaptively responds to environmental changes due to cardiac injury, but also provide insight into how flow-mediated mechanisms may regulate cardiomyocyte reprogramming and heart regeneration. eLife Sciences Publications, Ltd 2019-06-25 /pmc/articles/PMC6592682/ /pubmed/31237233 http://dx.doi.org/10.7554/eLife.44816 Text en © 2019, Gálvez-Santisteban et al http://creativecommons.org/licenses/by/4.0/ 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 Developmental Biology
Gálvez-Santisteban, Manuel
Chen, Danni
Zhang, Ruilin
Serrano, Ricardo
Nguyen, Cathleen
Zhao, Long
Nerb, Laura
Masutani, Evan M
Vermot, Julien
Burns, Charles Geoffrey
Burns, Caroline E
del Álamo, Juan C
Chi, Neil C
Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
title Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
title_full Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
title_fullStr Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
title_full_unstemmed Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
title_short Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
title_sort hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592682/
https://www.ncbi.nlm.nih.gov/pubmed/31237233
http://dx.doi.org/10.7554/eLife.44816
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