Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart.
Animals
Animals, Genetically Modified
Cell Proliferation
Cellular Reprogramming
/ genetics
Female
Gene Expression Regulation, Developmental
Genes, erbB-2
/ genetics
Glycolysis
Heart
/ embryology
Hexokinase
/ genetics
Male
Mice
Models, Animal
Myocardium
/ metabolism
Myocytes, Cardiac
/ cytology
Neuregulin-1
/ genetics
Regeneration
/ genetics
Signal Transduction
/ genetics
Single-Cell Analysis
/ methods
Zebrafish
/ embryology
Zebrafish Proteins
/ genetics
developmental biology
heart
metabolism
mouse
neuregulin
regeneration
regenerative medicine
stem cells
zebrafish
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
23 12 2019
23 12 2019
Historique:
received:
12
07
2019
accepted:
04
12
2019
pubmed:
24
12
2019
medline:
17
6
2020
entrez:
24
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31868166
doi: 10.7554/eLife.50163
pii: 50163
pmc: PMC7000220
doi:
pii:
Substances chimiques
Neuregulin-1
0
Nrg1 protein, mouse
0
Zebrafish Proteins
0
Hexokinase
EC 2.7.1.1
Banques de données
GEO
['GSE139218']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Human Frontier Science Program
ID : LT001404/2017-L
Pays : International
Organisme : ERC
ID : AdG788194
Pays : International
Organisme : ERC
ID : StG281289
Pays : International
Organisme : NIH Clinical Center
ID : RO1 HL081674
Pays : International
Organisme : Fondation Leducq Transatlantic Network of Excellence
ID : 15CVD03
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : 316249678
Pays : International
Organisme : Dutch Research Council
ID : 016.186.017-3
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL136182
Pays : United States
Organisme : European Molecular Biology Organization
ID : ALTF1129-2015
Pays : International
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : 016.186.017-3
Pays : International
Organisme : NICHD NIH HHS
ID : T32 HD040372
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131319
Pays : United States
Organisme : Deutsche Forschungsgemeinschaft
ID : 251293561
Pays : International
Organisme : Netherlands Heart Foundation NHS/CVON
ID : Cobra3
Pays : International
Organisme : ERA-CVD
ID : JCT2016-40-080
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : 414077062
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL081674
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019, Honkoop et al.
Déclaration de conflit d'intérêts
HH, Dd, AA, FK, AS, PN, Cd, LG, MM, AS, FT, JP, WN, AB, GW, GP, DG, Wv, JK, RJ, KP, Av, ET, JB No competing interests declared
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