PUBLICATION

Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Authors
Nguyen, P.D., Gooijers, I., Campostrini, G., Verkerk, A.O., Honkoop, H., Bouwman, M., de Bakker, D.E.M., Koopmans, T., Vink, A., Lamers, G.E.M., Shakked, A., Mars, J., Mulder, A.A., Chocron, S., Bartscherer, K., Tzahor, E., Mummery, C.L., de Boer, T.P., Bellin, M., Bakkers, J.
ID
ZDB-PUB-230519-27
Date
2023
Source
Science (New York, N.Y.)   380: 758764758-764 (Journal)
Registered Authors
Bakkers, Jeroen, Chocron, Sonja
Keywords
none
Datasets
GEO:GSE224156
MeSH Terms
  • Animals
  • Calcium*/physiology
  • Cell Proliferation
  • Heart*/physiology
  • Myocytes, Cardiac*/physiology
  • Regeneration*
  • Sarcomeres*/physiology
  • Zebrafish*/physiology
PubMed
37200435 Full text @ Science
Abstract
Zebrafish hearts can regenerate by replacing damaged tissue with new cardiomyocytes. Although the steps leading up to the proliferation of surviving cardiomyocytes have been extensively studied, little is known about the mechanisms that control proliferation and redifferentiation to a mature state. We found that the cardiac dyad, a structure that regulates calcium handling and excitation-contraction coupling, played a key role in the redifferentiation process. A component of the cardiac dyad called leucine-rich repeat-containing 10 (Lrrc10) acted as a negative regulator of proliferation, prevented cardiomegaly, and induced redifferentiation. We found that its function was conserved in mammalian cardiomyocytes. This study highlights the importance of the underlying mechanisms required for heart regeneration and their application to the generation of fully functional cardiomyocytes.
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