Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration
| Autor(en): | Nguyen, Phong D. Gooijers, Iris Campostrini, Giulia Verkerk, Arie O. Honkoop, Hessel Bouwman, Mara de Bakker, Dennis E. M. Koopmans, Tim Vink, Aryan Lamers, Gerda E. M. Shakked, Avraham Mars, Jonas Mulder, Aat A. Chocron, Sonja Bartscherer, Kerstin Tzahor, Eldad Mummery, Christine L. de Boer, Teun P. Bellin, Milena Bakkers, Jeroen |
Stichwörter: | CRYOINJURY; DEDIFFERENTIATION; LRRC10; Multidisciplinary Sciences; Science & Technology - Other Topics; ZEBRAFISH HEART REGENERATION | Erscheinungsdatum: | 2023 | Herausgeber: | AMER ASSOC ADVANCEMENT SCIENCE | Enthalten in: | SCIENCE | Band: | 380 | Ausgabe: | 6646 | Startseite: | 758 | Seitenende: | 764 | Zusammenfassung: | 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 excitationcontraction 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. |
ISSN: | 0036-8075 | DOI: | 10.1126/science.abo6718 |
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