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Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart

Authors :
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
Grun, Dominic
van der Laarse, Willem J
Klumperman, Judith
Jaspers, Richard T
Poss, Kenneth D
van Oudenaarden, Alexander
Tzahor, Eldad
Bakkers, Jeroen
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
Grun, Dominic
van der Laarse, Willem J
Klumperman, Judith
Jaspers, Richard T
Poss, Kenneth D
van Oudenaarden, Alexander
Tzahor, Eldad
Bakkers, Jeroen
Source :
eLife vol.8 (2019) date: 2019-12-23 [ISSN 2050-084X]
Publication Year :
2019

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.

Details

Database :
OAIster
Journal :
eLife vol.8 (2019) date: 2019-12-23 [ISSN 2050-084X]
Notes :
DOI: 10.7554/eLife.50163, eLife vol.8 (2019) date: 2019-12-23 [ISSN 2050-084X], English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1139318948
Document Type :
Electronic Resource