Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

• 成果类型: Article
• 署名作者: 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
• 署名单位: Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; University of Amsterdam; University of Amsterdam; Leibniz Association; Leibniz Institut fur Alternsforschung - Fritz-Lipmann-Institut (FLI); University Osnabruck; Utrecht University; Utrecht University Medical Center; Leiden University - Excl LUMC; Leiden University; Weizmann Institute of Science; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Utrecht University; Utrecht University Medical Center; University of Padua; Veneto Institute Molecular Medicine; Utrecht University; Utrecht University Medical Center
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8227
• DOI: 10.1126/science.abo6718
• 发表日期: 2023-05-19
• 页码: 758-764
• 关键词: zebrafish heart regeneration; dedifferentiation; cryoinjury; lrrc10

摘要

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.