Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.50163
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Categories
Funding
- ERA-CVD [JCT2016-40-080]
- Deutsche Forschungsgemeinschaft [251293561, 316249678, 414077062]
- Netherlands Heart Foundation NHS/CVON
- European Molecular Biology Organization [ALTF1129-2015]
- Human Frontier Science Program [LT001404/2017-L]
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek [016.186.017-3]
- NIH Clinical Center [RO1 HL081674, R01 HL131319, R01 HL136182]
- ERC [StG281289, AdG788194]
- Fondation Leducq Transatlantic Network of Excellence [15CVD03]
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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.
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