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Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart
While the heart regenerates poorly in mammals, efficient heart regeneration occurs in zebrafish. Studies in zebrafish have resulted in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. To identify which processes occur in prolife...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000220/ https://www.ncbi.nlm.nih.gov/pubmed/31868166 http://dx.doi.org/10.7554/eLife.50163 |
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author | Honkoop, Hessel de Bakker, Dennis EM Aharonov, Alla Kruse, Fabian Shakked, Avraham Nguyen, Phong D de Heus, Cecilia Garric, Laurence Muraro, Mauro J Shoffner, Adam Tessadori, Federico Peterson, Joshua Craiger Noort, Wendy Bertozzi, Alberto Weidinger, Gilbert Posthuma, George Grün, Dominic van der Laarse, Willem J Klumperman, Judith Jaspers, Richard T Poss, Kenneth D van Oudenaarden, Alexander Tzahor, Eldad Bakkers, Jeroen |
author_facet | Honkoop, Hessel de Bakker, Dennis EM Aharonov, Alla Kruse, Fabian Shakked, Avraham Nguyen, Phong D de Heus, Cecilia Garric, Laurence Muraro, Mauro J Shoffner, Adam Tessadori, Federico Peterson, Joshua Craiger Noort, Wendy Bertozzi, Alberto Weidinger, Gilbert Posthuma, George Grün, Dominic van der Laarse, Willem J Klumperman, Judith Jaspers, Richard T Poss, Kenneth D van Oudenaarden, Alexander Tzahor, Eldad Bakkers, Jeroen |
author_sort | Honkoop, Hessel |
collection | PubMed |
description | While the heart regenerates poorly in mammals, efficient heart regeneration occurs in zebrafish. Studies in zebrafish have resulted in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. To identify which processes occur in proliferating cardiomyocytes we have used a single-cell RNA-sequencing approach. We uncovered that proliferating border zone cardiomyocytes have very distinct transcriptomes compared to the nonproliferating remote cardiomyocytes and that they resemble embryonic cardiomyocytes. Moreover, these cells have reduced expression of mitochondrial genes and reduced mitochondrial activity, while glycolysis gene expression and glucose uptake are increased, indicative for metabolic reprogramming. Furthermore, we find that the metabolic reprogramming of border zone cardiomyocytes is induced by Nrg1/ErbB2 signaling and is important for their proliferation. This mechanism is conserved in murine hearts in which cardiomyocyte proliferation is induced by activating ErbB2 signaling. Together these results demonstrate that glycolysis regulates cardiomyocyte proliferation during heart regeneration. |
format | Online Article Text |
id | pubmed-7000220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-70002202020-02-06 Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart Honkoop, Hessel de Bakker, Dennis EM Aharonov, Alla Kruse, Fabian Shakked, Avraham Nguyen, Phong D de Heus, Cecilia Garric, Laurence Muraro, Mauro J Shoffner, Adam Tessadori, Federico Peterson, Joshua Craiger Noort, Wendy Bertozzi, Alberto Weidinger, Gilbert Posthuma, George Grün, Dominic van der Laarse, Willem J Klumperman, Judith Jaspers, Richard T Poss, Kenneth D van Oudenaarden, Alexander Tzahor, Eldad Bakkers, Jeroen eLife Developmental Biology While the heart regenerates poorly in mammals, efficient heart regeneration occurs in zebrafish. Studies in zebrafish have resulted in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. To identify which processes occur in proliferating cardiomyocytes we have used a single-cell RNA-sequencing approach. We uncovered that proliferating border zone cardiomyocytes have very distinct transcriptomes compared to the nonproliferating remote cardiomyocytes and that they resemble embryonic cardiomyocytes. Moreover, these cells have reduced expression of mitochondrial genes and reduced mitochondrial activity, while glycolysis gene expression and glucose uptake are increased, indicative for metabolic reprogramming. Furthermore, we find that the metabolic reprogramming of border zone cardiomyocytes is induced by Nrg1/ErbB2 signaling and is important for their proliferation. This mechanism is conserved in murine hearts in which cardiomyocyte proliferation is induced by activating ErbB2 signaling. Together these results demonstrate that glycolysis regulates cardiomyocyte proliferation during heart regeneration. eLife Sciences Publications, Ltd 2019-12-23 /pmc/articles/PMC7000220/ /pubmed/31868166 http://dx.doi.org/10.7554/eLife.50163 Text en © 2019, Honkoop 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 Honkoop, Hessel de Bakker, Dennis EM Aharonov, Alla Kruse, Fabian Shakked, Avraham Nguyen, Phong D de Heus, Cecilia Garric, Laurence Muraro, Mauro J Shoffner, Adam Tessadori, Federico Peterson, Joshua Craiger Noort, Wendy Bertozzi, Alberto Weidinger, Gilbert Posthuma, George Grün, Dominic van der Laarse, Willem J Klumperman, Judith Jaspers, Richard T Poss, Kenneth D van Oudenaarden, Alexander Tzahor, Eldad Bakkers, Jeroen Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart |
title | Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart |
title_full | Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart |
title_fullStr | Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart |
title_full_unstemmed | Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart |
title_short | Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart |
title_sort | single-cell analysis uncovers that metabolic reprogramming by erbb2 signaling is essential for cardiomyocyte proliferation in the regenerating heart |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000220/ https://www.ncbi.nlm.nih.gov/pubmed/31868166 http://dx.doi.org/10.7554/eLife.50163 |
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