Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart
Honkoop H, De Bakker DEM, Aharonov A, Kruse F, Shakked A, Nguyen PD, De Heus C, Garric L, Muraro MJ, Shoffner A, Tessadori F, Peterson JC, Noort W, Bertozzi A, Weidinger G, Posthuma G, Grun D, Van Der Laarse WJ, Klumperman J, Jaspers RT, Poss KD, Van Oudenaarden A, Tzahor E, Bakkers J (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 8
Article Number: e50163
DOI: 10.7554/eLife.50163
Abstract
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.
Involved external institutions
Hubrecht Institute
Netherlands (NL)
University Medical Centre Utrecht (UMC Utrecht)
Netherlands (NL)
Vrije Universiteit Amsterdam (VU) / University Amsterdam
Netherlands (NL)
Universität Ulm
Germany (DE)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics
Germany (DE)
Duke University
United States (USA) (US)
Netherlands (NL)
University Medical Centre Utrecht (UMC Utrecht)
Netherlands (NL)
Vrije Universiteit Amsterdam (VU) / University Amsterdam
Netherlands (NL)
Universität Ulm
Germany (DE)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics
Germany (DE)
Duke University
United States (USA) (US)
How to cite
APA:
Honkoop, H., De Bakker, D.E.M., Aharonov, A., Kruse, F., Shakked, A., Nguyen, P.D.,... Bakkers, J. (2019). Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart. eLife, 8. https://doi.org/10.7554/eLife.50163
MLA:
Honkoop, Hessel, et al. "Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart." eLife 8 (2019).
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