Reversible reprogramming of cardiomyocytes to a fetal state drives heart 
regeneration in mice

Chen, Yanpu; Luttmann, Felipe F.; Schoger, Eric; Schoeler, Hans R.; Zelarayan, Laura C.; Kim, Kee-Pyo; Haigh, Jody J.; Kim, Johnny; Braun, Thomas

doi:10.1126/science.abg5159

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Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice

MPS-Authors

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Chen, Yanpu
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Luttmann, Felipe F.
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Kim, Johnny
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Braun, Thomas
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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引用

Chen, Y., Luttmann, F. F., Schoger, E., Schoeler, H. R., Zelarayan, L. C., Kim, K.-P., Haigh, J. J., Kim, J., & Braun, T. (2021). Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice. SI, 373(6562), 1537-1540. doi:10.1126/science.abg5159.

引用: https://hdl.handle.net/21.11116/0000-0009-51B8-C

要旨

Cardiomyocyte (CM) replacement is very slow in adultmammalian hearts, preventing regeneration of damaged myocardium. By contrast, fetal hearts display considerable regenerative potential owing to the presence of less mature CMs that still have the ability to proliferate. In this study, we demonstrate that heart-specific expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) induces adult CMs to dedifferentiate, conferring regenerative capacity to adult hearts. Transient, CM-specific expression of OSKM extends the regenerative window for postnatal mouse hearts and induces a gene expression program in adult CMs that resembles that of fetal CMs. Extended expression of OSKM in CMs leads to cellular reprogramming and heart tumor formation. Short-term OSKM expression before and during myocardial infarction ameliorates myocardial damage and improves cardiac function, demonstrating that temporally controlled dedifferentiation and reprogramming enable cell cycle reentry of mammalian CMs and facilitate heart regeneration.