Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells

被引：55

作者：

Tosic, Milica ^{[1
,2
]}

Allen, Anita ^{[1
,2
]}

Willmann, Dominica ^{[1
,2
]}

Lepper, Christoph ^{[3
]}

Kim, Johnny ^{[4
]}

Duteil, Delphine ^{[1
,2
]}

Schuele, Roland ^{[1
,2
,5
,6
,7
]}

机构：

[1] Albert Ludwigs Univ Freiburg, Univ Klinikum Freiburg, Med Fak, Urol Klin, Breisacherstr 66, D-79106 Freiburg, Germany

[2] Albert Ludwigs Univ Freiburg, Univ Klinikum Freiburg, Med Fak, Zent Klin Forsch, Breisacherstr 66, D-79106 Freiburg, Germany

[3] Carnegie Inst, Dept Embryol, 3520 San Martin Dr, Baltimore, MD 21218 USA

[4] Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, Ludwigstr 43, D-61231 Bad Nauheim, Germany

[5] Albert Ludwigs Univ, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany

[6] Deutsch Konsortium Translat Krebsforsch, D-79106 Freiburg, Germany

[7] K Met GmbH, Breisacherstr 66, D-79106 Freiburg, Germany

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

欧洲研究理事会;

关键词：

TRANSCRIPTION; DIFFERENTIATION; EXPRESSION; SPECIFICATION; METHYLATION; MYOGENESIS; REVEALS; FUSION; PAX7;

D O I：

10.1038/s41467-017-02740-5

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：

Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.

引用

页数：14

共 49 条

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