澳大利亚维克多·张心脏研究所Kazu Kikuchi团队在研究中取得进展。他们最新研究揭示Krüppel样因子1是斑马鱼核心心肌生成触发因子。2021年4月9日出版的《科学》杂志发表了这项成果。

他们确定了Krüppel样因子1（Klf1 / Eklf）的强大心肌发生作用，该因子在成年斑马鱼心肌中受到损伤后被诱导。Klf1心肌功能抑制不会影响心脏发育，但会严重损害再生能力。瞬时Klf1激活足以在未受损的心脏中扩展成熟的心肌。

Klf1指导心脏转录因子网络的表观遗传重编程，从而促使协调的心肌细胞去分化和增殖。Klf1诱导的线粒体代谢从氧化呼吸到合成代谢途径的重新连接支持了心肌的扩张。他们的发现将Klf1确立为成年斑马鱼心脏核心心肌细胞更新的核心转录调节因子。

研究人员表示，心脏再生需要成熟心肌细胞去分化和增殖，但这种可塑性机制尚不清楚。

附：英文原文

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

Author: Masahito Ogawa, Fan-Suo Geng, David T. Humphreys, Esther Kristianto, Delicia Z. Sheng, Subhra P. Hui, Yuxi Zhang, Kotaro Sugimoto, Maki Nakayama, Dawei Zheng, Daniel Hesselson, Mark P. Hodson, Ozren Bogdanovic, Kazu Kikuchi

Issue&Volume: 2021/04/09

Abstract: 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.

DOI: 10.1126/science.abe2762

Source: https://science.sciencemag.org/content/372/6538/201