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12 results on '"Honkoop, Hessel"'

1. Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Author

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

Published
2023
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2. Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Author

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, 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, and Bakkers, Jeroen

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.

Published
2023

3. Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Author

Medische Fysiologie, Pathologie Pathologen staf, Circulatory Health, Child Health, Onderzoek, Cardiologie onderzoek 2, 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, Medische Fysiologie, Pathologie Pathologen staf, Circulatory Health, Child Health, Onderzoek, Cardiologie onderzoek 2, 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, and Bakkers, Jeroen

Published
2023

4. Uncovering the road towards cardiomyocyte proliferation: Temporal and spatial analysis of heart regeneration in zebrafish

Author

Honkoop, Hessel, Bakkers, J.P.W.M., and University Utrecht

Subjects
zebrafish, heart, regeneration, metabolism, sequencing, proliferation, imaging
Abstract

Myocardial infarctions are a major cause of death in the Western world. During such an event the heart loses millions of cardiomyocytes resulting from a lack of oxygen and nutrients. Since adult human cardiomyocytes are considered post-mitotic and replace lost tissue, the damaged tissue is replaced by a permanent scar. This scar does not contribute to contractions and as, a consequence, myocardial infarction patients frequently suffer from heart failure. To combat this, there is a need for new ways to replace the lost cardiac tissue. Opposite to humans, the zebrafish holds the unique capacity to replace the lost cardiomyocytes after cardiac damage. To achieve this the zebrafish makes use of a layer of surviving cardiomyocytes directly adjacent to the injury. We will call this region the border zone from now. The cardiomyocytes in this border zone start to proliferate after injury and produce new myocardial tissue that will eventually repopulate the injury area and restore cardiac function. In this thesis we used to zebrafish to study this special population of proliferating cardiomyocytes based on the premise that knowledge obtained from this cell population holds the potential to boost human cardiomyocyte proliferation as well. For this, we made use of microscopy and sequencing techniques to study the changes these cells undergo leading to proliferation at a single cell level. Doing so, we were the first to describe changes in sarcomeres and metabolism during the process of adult cardiomyocyte proliferation. Moreover, we generated a transcriptomic roadmap towards cardiomyocyte proliferation and identified novel targets that hold the potential to boost this process. For one of these factors we additionally confirmed its importance for successful heart regeneration. In conclusion, we used a live imaging and transcriptomic techniques at the single cell level to study border zone cardiomyocytes prior to and during proliferation. The knowledge we obtain in this thesis on these cells holds promise to stimulate cardiomyocyte proliferation in humans as well and boost heart regeneration after myocardial damage.

Published
2022

7. Live imaging of adult zebrafish cardiomyocyte proliferation ex vivo

Author

Honkoop, Hessel, Nguyen, Phong D, van der Velden, Veronique E M, Sonnen, Katharina F, Bakkers, Jeroen, Honkoop, Hessel, Nguyen, Phong D, van der Velden, Veronique E M, Sonnen, Katharina F, and Bakkers, Jeroen

Abstract

Zebrafish are excellent at regenerating their heart by reinitiating proliferation in pre-existing cardiomyocytes. Studying how zebrafish achieve this holds great potential in developing new strategies to boost mammalian heart regeneration. Nevertheless, the lack of appropriate live-imaging tools for the adult zebrafish heart has limited detailed studies into the dynamics underlying cardiomyocyte proliferation. Here, we address this by developing a system in which cardiac slices of the injured zebrafish heart are cultured ex vivo for several days while retaining key regenerative characteristics, including cardiomyocyte proliferation. In addition, we show that the cardiac slice culture system is compatible with live timelapse imaging and allows manipulation of regenerating cardiomyocytes with drugs that normally would have toxic effects that prevent their use. Finally, we use the cardiac slices to demonstrate that adult cardiomyocytes with fully assembled sarcomeres can partially disassemble their sarcomeres in a calpain- and proteasome-dependent manner to progress through nuclear division and cytokinesis. In conclusion, we have developed a cardiac slice culture system, which allows imaging of native cardiomyocyte dynamics in real time to discover cellular mechanisms during heart regeneration.

Published
2021

8. Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart

Author

Honkoop, Hessel, de Bakker, Dennis Em, Aharonov, Alla, Kruse, Fabian, Shakked, Avraham, Nguyen, Phong D, de Heus, Cecilia, Garric, Laurence, Muraro, Mauro J, Shoffner, Adam, Tessadori, Federico, Peterson, Joshua Craiger, Noort, Wendy, Bertozzi, Alberto, Weidinger, Gilbert, Posthuma, George, Grun, Dominic, van der Laarse, Willem J, Klumperman, Judith, Jaspers, Richard T, Poss, Kenneth D, van Oudenaarden, Alexander, Tzahor, Eldad, Bakkers, Jeroen, Honkoop, Hessel, de Bakker, Dennis Em, Aharonov, Alla, Kruse, Fabian, Shakked, Avraham, Nguyen, Phong D, de Heus, Cecilia, Garric, Laurence, Muraro, Mauro J, Shoffner, Adam, Tessadori, Federico, Peterson, Joshua Craiger, Noort, Wendy, Bertozzi, Alberto, Weidinger, Gilbert, Posthuma, George, Grun, Dominic, van der Laarse, Willem J, Klumperman, Judith, Jaspers, Richard T, Poss, Kenneth D, van Oudenaarden, Alexander, Tzahor, Eldad, and Bakkers, Jeroen

Abstract

While the heart regenerates poorly in mammals, efficient heart regeneration occurs in zebrafish. Studies in zebrafish have resulted in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. To identify which processes occur in proliferating cardiomyocytes we have used a single-cell RNA-sequencing approach. We uncovered that proliferating border zone cardiomyocytes have very distinct transcriptomes compared to the nonproliferating remote cardiomyocytes and that they resemble embryonic cardiomyocytes. Moreover, these cells have reduced expression of mitochondrial genes and reduced mitochondrial activity, while glycolysis gene expression and glucose uptake are increased, indicative for metabolic reprogramming. Furthermore, we find that the metabolic reprogramming of border zone cardiomyocytes is induced by Nrg1/ErbB2 signaling and is important for their proliferation. This mechanism is conserved in murine hearts in which cardiomyocyte proliferation is induced by activating ErbB2 signaling. Together these results demonstrate that glycolysis regulates cardiomyocyte proliferation during heart regeneration.

Published
2019

9. Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart

Author

Medische Fysiologie, Cancer, CMM Groep Klumperman, Child Health, Genetica Groep Van Haaften, CMM Sectie Celbiologie, Regenerative Medicine and Stem Cells, Brain, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Circulatory Health, Honkoop, Hessel, de Bakker, Dennis Em, Aharonov, Alla, Kruse, Fabian, Shakked, Avraham, Nguyen, Phong D, de Heus, Cecilia, Garric, Laurence, Muraro, Mauro J, Shoffner, Adam, Tessadori, Federico, Peterson, Joshua Craiger, Noort, Wendy, Bertozzi, Alberto, Weidinger, Gilbert, Posthuma, George, Grun, Dominic, van der Laarse, Willem J, Klumperman, Judith, Jaspers, Richard T, Poss, Kenneth D, van Oudenaarden, Alexander, Tzahor, Eldad, Bakkers, Jeroen, Medische Fysiologie, Cancer, CMM Groep Klumperman, Child Health, Genetica Groep Van Haaften, CMM Sectie Celbiologie, Regenerative Medicine and Stem Cells, Brain, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Circulatory Health, Honkoop, Hessel, de Bakker, Dennis Em, Aharonov, Alla, Kruse, Fabian, Shakked, Avraham, Nguyen, Phong D, de Heus, Cecilia, Garric, Laurence, Muraro, Mauro J, Shoffner, Adam, Tessadori, Federico, Peterson, Joshua Craiger, Noort, Wendy, Bertozzi, Alberto, Weidinger, Gilbert, Posthuma, George, Grun, Dominic, van der Laarse, Willem J, Klumperman, Judith, Jaspers, Richard T, Poss, Kenneth D, van Oudenaarden, Alexander, Tzahor, Eldad, and Bakkers, Jeroen

Published
2019

10. Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart

Author

Honkoop, Hessel, primary, de Bakker, Dennis EM, additional, Aharonov, Alla, additional, Kruse, Fabian, additional, Shakked, Avraham, additional, Nguyen, Phong D, additional, de Heus, Cecilia, additional, Garric, Laurence, additional, Muraro, Mauro J, additional, Shoffner, Adam, additional, Tessadori, Federico, additional, Peterson, Joshua Craiger, additional, Noort, Wendy, additional, Bertozzi, Alberto, additional, Weidinger, Gilbert, additional, Posthuma, George, additional, Grün, Dominic, additional, van der Laarse, Willem J, additional, Klumperman, Judith, additional, Jaspers, Richard T, additional, Poss, Kenneth D, additional, van Oudenaarden, Alexander, additional, Tzahor, Eldad, additional, and Bakkers, Jeroen, additional

Published
2019
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11. Author response: Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart

Author

Honkoop, Hessel, primary, de Bakker, Dennis EM, additional, Aharonov, Alla, additional, Kruse, Fabian, additional, Shakked, Avraham, additional, Nguyen, Phong D, additional, de Heus, Cecilia, additional, Garric, Laurence, additional, Muraro, Mauro J, additional, Shoffner, Adam, additional, Tessadori, Federico, additional, Peterson, Joshua Craiger, additional, Noort, Wendy, additional, Bertozzi, Alberto, additional, Weidinger, Gilbert, additional, Posthuma, George, additional, Grün, Dominic, additional, van der Laarse, Willem J, additional, Klumperman, Judith, additional, Jaspers, Richard T, additional, Poss, Kenneth D, additional, van Oudenaarden, Alexander, additional, Tzahor, Eldad, additional, and Bakkers, Jeroen, additional

Published
2019
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12. A metabolic switch from OXPHOS to glycolysis is essential for cardiomyocyte proliferation in the regenerating heart

Author

Honkoop, Hessel, primary, de Bakker, Dennis, additional, Aharonov, Alla, additional, Kruse, Fabian, additional, Shakked, Avraham, additional, Nguyen, Phong, additional, de Heus, Cecilia, additional, Garric, Laurence, additional, Muraro, Mauro, additional, Shoffner, Adam, additional, Tessadori, Federico, additional, Peterson, Joshua, additional, Noort, Wendy, additional, Posthuma, George, additional, Grun, Dominic, additional, van der Laarse, Willem, additional, Klumperman, Judith, additional, Jaspers, Richard, additional, Poss, Kenneth, additional, van Oudenaarden, Alexander, additional, Tzahor, Eldad, additional, and Bakkers, Jeroen, additional

Published
2018
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