Kruppel-like factor 1 is a core cardiomyogenic trigger in zebrafish
Kruppel-like factor 1 is a core cardiomyogenic trigger in zebrafish
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DOI：
10.1126/science.abe2762
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发表时间：
2021-04-09
期刊：
影响因子：
56.9
通讯作者：
Kikuchi, Kazu
中科院分区：
文献类型：
--
作者：
Ogawa, Masahito;Geng, Fan-Suo;Kikuchi, Kazu
心脏再生需要成熟心肌细胞的去分化和增殖，但这种可塑性的机制尚不清楚。在这里，我们确定了kruppel样因子1 （Klf1/Eklf）在成年斑马鱼损伤心肌中诱导的强大的心肌生成作用。心肌抑制Klf1功能不影响心脏发育，但严重损害心脏再生。短暂的Klf1激活足以扩大未损伤心脏的成熟心肌。Klf1指导心脏转录因子网络的表观遗传重编程，允许协调的心肌细胞去分化和增殖。心肌扩张是由klf1诱导的线粒体代谢从氧化呼吸到合成代谢途径的重新布线所支持的。我们的研究结果表明，Klf1是成年斑马鱼心脏中心肌细胞更新的核心转录调节因子。
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.