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

doi:https://doi.org/10.1126/science.abo6718

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

Research output: Contribution to journal › Article › Academic › peer-review

4 Citations (Scopus)

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.

Original language	English
Pages (from-to)	758-764
Number of pages	7
Journal	Science
Volume	380
Issue number	6646
DOIs	https://doi.org/10.1126/science.abo6718
Publication status	Published - 19 May 2023

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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. (2023). Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration. Science, 380(6646), 758-764. https://doi.org/10.1126/science.abo6718

@article{ef05d25e9f8a413eb8aec1ba023cfed5,

title = "Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration",

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.",

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

year = "2023",

month = may,

day = "19",

doi = "https://doi.org/10.1126/science.abo6718",

language = "English",

volume = "380",

pages = "758--764",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6646",

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Nguyen, PD, Gooijers, I, Campostrini, G, Verkerk, AO, Honkoop, H, Bouwman, M, de Bakker, DEM, Koopmans, T, Vink, A, Lamers, GEM, Shakked, A, Mars, J, Mulder, AA, Chocron, S, Bartscherer, K, Tzahor, E, Mummery, CL, de Boer, TP, Bellin, M & Bakkers, J 2023, 'Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration', Science, vol. 380, no. 6646, pp. 758-764. https://doi.org/10.1126/science.abo6718

TY - JOUR

T1 - Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

AU - Nguyen, Phong D.

AU - Gooijers, Iris

AU - Campostrini, Giulia

AU - Verkerk, Arie O.

AU - Honkoop, Hessel

AU - Bouwman, Mara

AU - de Bakker, Dennis E. M.

AU - Koopmans, Tim

AU - Vink, Aryan

AU - Lamers, Gerda E. M.

AU - Shakked, Avraham

AU - Mars, Jonas

AU - Mulder, Aat A.

AU - Chocron, Sonja

AU - Bartscherer, Kerstin

AU - Tzahor, Eldad

AU - Mummery, Christine L.

AU - de Boer, Teun P.

AU - Bellin, Milena

AU - Bakkers, Jeroen

PY - 2023/5/19

Y1 - 2023/5/19

N2 - 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.

AB - 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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U2 - https://doi.org/10.1126/science.abo6718

DO - https://doi.org/10.1126/science.abo6718

M3 - Article

C2 - 37200435

SN - 0036-8075

VL - 380

SP - 758

EP - 764

JO - Science

JF - Science

IS - 6646

ER -

Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Abstract

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