@article{1887be2fcbfa49c28276320664ef9642,
title = "Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart",
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.",
keywords = "RESEARCH ARTICLE, DEVELOPMENTAL BIOLOGY, STEM CELLS AND REGENERATIVE MEDICINE, regeneration, heart, metabolism, zebrafish, mouse, neuregulin",
author = "Hessel Honkoop and {de Bakker}, {Dennis Em} and Alla Aharonov and Fabian Kruse and Avraham Shakked and Nguyen, {Phong D} and {de Heus}, Cecilia and Laurence Garric and Muraro, {Mauro J} and Adam Shoffner and Federico Tessadori and Peterson, {Joshua Craiger} and Wendy Noort and Alberto Bertozzi and Gilbert Weidinger and George Posthuma and Dominic Grun and {van der Laarse}, {Willem J} and Judith Klumperman and Jaspers, {Richard T} and Poss, {Kenneth D} and {van Oudenaarden}, Alexander and Eldad Tzahor and Jeroen Bakkers",
note = "Funding Information: Funding: J.B. acknowledges support from the Netherlands Cardiovascular Research Funding Information: and ERA-CVD grant CARDIO-PRO JCT2016-40-080. L.G. was supported by an EMBO Funding Information: Initiative and the Dutch Heart Foundation (grants CVON2011-12 HUSTCARE and Cobra3) Funding Information: (016.186.017-3). G.W. was funded by the Deutsche Forschungsgemeinschaft (SFB 1149, Funding Information: We would like to thank V. Christoffels for critical reading of the manuscript and Life Science Editors for editing support. Funding: J.B. acknowledges support from the Netherlands Cardiovascular Research Initiative and the Dutch Heart Foundation (grants CVON2011-12 HUSTCARE and Cobra3) and ERA-CVD grant CARDIO-PRO JCT2016-40-080. L.G. was supported by an EMBO long-term fellowship. P.D.N. is supported by an EMBO Long Term Fellowship ALTF1129-2015, HFSPO Fellowship (LT001404/2017-L) and a NWO-ZonMW Veni grant (016.186.017-3). G.W. was funded by the Deutsche Forschungsgemeinschaft (SFB 1149, project number 251293561; SFB 1279, project number 316249678; WE 4223/6-1, project number 414077062) and by the BMBF (EU ERA-CVD {"}Cardio-Pro{"}, grant number 01KL1704). K.D.P. acknowledges support from the American Heart Association, Foundation Leducq, and NIH (R01 HL081674, R01 HL131319, and R01 HL136182). Funding Information: long-term fellowship. P.D.N. is supported by an EMBO Long Term Fellowship ALTF1129- Funding Information: 01KL1704). K.D.P. acknowledges support from the American Heart Association, Foundation Publisher Copyright: {\textcopyright} 2019, eLife Sciences Publications Ltd. All rights reserved.",
year = "2019",
month = dec,
day = "23",
doi = "10.7554/eLife.50163",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}