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

被引：47

作者：

Ogawa, Masahito ^{[1
,2
]}

Geng, Fan-Suo ^{[3
,4
]}

Humphreys, David T. ^{[4
,5
]}

Kristianto, Esther ^{[6
]}

Sheng, Delicia Z. ^{[1
]}

Hui, Subhra P. ^{[1
]}

Zhang, Yuxi ^{[7
]}

Sugimoto, Kotaro ^{[1
]}

Nakayama, Maki ^{[1
]}

Zheng, Dawei ^{[1
]}

Hesselson, Daniel ^{[4
,7
,8
,9
]}

Hodson, Mark P. ^{[6
,10
]}

Bogdanovic, Ozren ^{[3
,11
]}

Kikuchi, Kazu ^{[1
,2
,4
]}

机构：

[1] Victor Chang Cardiac Res Inst, Dev & Stem Cell Biol Div, Darlinghurst, NSW, Australia

[2] Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Regenerat Med & Tissue Engn, Osaka, Japan

[3] Garvan Inst Med Res, Genom & Epigenet Div, Darlinghurst, NSW, Australia

[4] Univ New South Wales Sydney, St Vincents Clin Sch, Kensington, NSW, Australia

[5] Victor Chang Cardiac Res Inst, Mol Struct & Computat Biol Div, Darlinghurst, NSW, Australia

[6] Freedman Fdn Metabol Facil, Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia

[7] Garvan Inst Med Res, Diabet & Metab Div, Darlinghurst, NSW, Australia

[8] Univ Sydney, Centenary Inst, Newtown, NSW, Australia

[9] Univ Sydney, Fac Med & Hlth, Newtown, NSW, Australia

[10] Univ Queensland, Sch Pharm, Woolloongabba, Qld, Australia

[11] Univ New South Wales Sydney, Sch Biotechnol & Biomol Sci, Kensington, NSW, Australia

来源：

SCIENCE | 2021年 / 372卷 / 6538期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

HEART REGENERATION; CELLS; CHROMATIN;

D O I：

10.1126/science.abe2762

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：201 / +

页数：39

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