Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration | Zendy

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

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Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Author(s) -

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

Publication year - 2023

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.abo6718

Subject(s) - microbiology and biotechnology , regeneration (biology) , zebrafish , sarcomere , calcium , regulator , biology , myocyte , chemistry , anatomy , biochemistry , organic chemistry , gene

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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