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Kruppel-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 Kruppel-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.

Type Journal
ISBN 1095-9203 (Electronic) 0036-8075 (Linking)
Authors Ogawa, M.; Geng, F. S.; Humphreys, D. T.; Kristianto, E.; Sheng, D. Z.; Hui, S. P.; Zhang, Y.; Sugimoto, K.; Nakayama, M.; Zheng, D.; Hesselson, D.; Hodson, M. P.; Bogdanovic, O.; Kikuchi, K.
Responsible Garvan Author A/Prof Ozren Bogdanovic
Publisher Name SCIENCE
Published Date 2021-04-30
Published Volume 372
Published Issue 6538
Published Pages 201-205
Status Published in-print
DOI 10.1126/science.abe2762
URL link to publisher's version