Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Phong D Nguyen, Iris Gooijers, Giulia Campostrini, Arie O Verkerk, Hessel Honkoop, Mara Bouwman, Dennis E M de Bakker, Tim Koopmans, Aryan Vink, Gerda E M Lamers, Avraham Shakked, Jonas Mars, Aat A Mulder, Sonja Chocron, Kerstin Bartscherer, Eldad Tzahor, Christine L Mummery, Teun P de Boer, Milena Bellin, Jeroen Bakkers

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

12 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)758-764
Aantal pagina's7
TijdschriftScience
Volume380
Nummer van het tijdschrift6646
DOI's
StatusGepubliceerd - 19 mei 2023

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