Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish

Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury....

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Published in:Science (American Association for the Advancement of Science) Vol. 372; no. 6538; p. 201
Main Authors: Ogawa, Masahito, Geng, Fan-Suo, Humphreys, David T, Kristianto, Esther, Sheng, Delicia Z, Hui, Subhra P, Zhang, Yuxi, Sugimoto, Kotaro, Nakayama, Maki, Zheng, Dawei, Hesselson, Daniel, Hodson, Mark P, Bogdanovic, Ozren, Kikuchi, Kazu
Format: Journal Article
Language:English
Published: United States 09.04.2021
Subjects:
Animals
Cardiomegaly, Exercise-Induced
Cell Dedifferentiation
Cell Differentiation
Cell Proliferation
Cellular Reprogramming
Gene Expression Regulation
Gene Regulatory Networks
Glycolysis
Heart - embryology
Heart - physiology
Heart Ventricles - cytology
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
Muscle Development
Myocardium - metabolism
Myocytes, Cardiac - cytology
Myocytes, Cardiac - physiology
Pentose Phosphate Pathway
Regeneration
Zebrafish
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary:Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury. Myocardial inhibition of Klf1 function does not affect heart development, but it severely impairs regeneration. Transient Klf1 activation is sufficient to expand mature myocardium in uninjured hearts. Klf1 directs epigenetic reprogramming of the cardiac transcription factor network, permitting coordinated cardiomyocyte dedifferentiation and proliferation. Myocardial expansion is supported by Klf1-induced rewiring of mitochondrial metabolism from oxidative respiration to anabolic pathways. Our findings establish Klf1 as a core transcriptional regulator of cardiomyocyte renewal in adult zebrafish hearts.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.abe2762