METTL3-Mediated m6A Methylation Regulates Muscle Stem Cells and Muscle Regeneration by Notch Signaling Pathway

被引：46

作者：

Liang, Yu ^{[1
,2
]}

Han, Hui ^{[1
]}

Xiong, Qiuchan ^{[3
,4
]}

Yang, Chunlong ^{[1
]}

Wang, Lu ^{[1
]}

Ma, Jieyi ^{[1
]}

Lin, Shuibin ^{[1
]}

Jiang, Yi-Zhou ^{[2
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 1, Inst Precis Med, Ctr Translat Med, Guangzhou 510080, Peoples R China

[2] Shenzhen Univ, Inst Adv Study, Shenzhen 518057, Peoples R China

[3] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610065, Peoples R China

[4] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610065, Peoples R China

来源：

STEM CELLS INTERNATIONAL | 2021年 / 2021卷

基金：

中国国家自然科学基金;

关键词：

RNA-METHYLATION; SATELLITE CELLS; N-6-METHYLADENOSINE; FATE; TRANSLATION;

D O I：

10.1155/2021/9955691

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The Pax7+ muscle stem cells (MuSCs) are essential for skeletal muscle homeostasis and muscle regeneration upon injury, while the molecular mechanisms underlying muscle stem cell fate determination and muscle regeneration are still not fully understood. N6-methyladenosine (m(6)A) RNA modification is catalyzed by METTL3 and plays important functions in posttranscriptional gene expression regulation and various biological processes. Here, we generated muscle stem cell-specific METTL3 conditional knockout mouse model and revealed that METTL3 knockout in muscle stem cells significantly inhibits the proliferation of muscle stem cells and blocks the muscle regeneration after injury. Moreover, knockin of METTL3 in muscle stem cells promotes the muscle stem cell proliferation and muscle regeneration in vivo. Mechanistically, METTL3-m(6)A-YTHDF1 axis regulates the mRNA translation of Notch signaling pathway. Our data demonstrated the important in vivo physiological function of METTL3-mediated m(6)A modification in muscle stem cells and muscle regeneration, providing molecular basis for the therapy of stem cell-related muscle diseases.

引用

页数：13

共 32 条

[1] MLL1 is required for PAX7 expression and satellite cell self-renewal in mice [J].

Addicks, Gregory C. ;

Brun, Caroline E. ;

Sincennes, Marie-Claude ;

Saber, John ;

Porter, Christopher J. ;

Stewart, A. Francis ;

Ernst, Patricia ;

Rudnicki, Michael A. .

NATURE COMMUNICATIONS, 2019, 10 (1)

[2] Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease [J].

Almada, Albert E. ;

Wagers, Amy J. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2016, 17 (05) :267-279

[3] m6A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells [J].

Batista, Pedro J. ;

Molinie, Benoit ;

Wang, Jinkai ;

Qu, Kun ;

Zhang, Jiajing ;

Li, Lingjie ;

Bouley, Donna M. ;

Lujan, Ernesto ;

Haddad, Bahareh ;

Daneshvar, Kaveh ;

Carter, Ava C. ;

Flynn, Ryan A. ;

Zhou, Chan ;

Lim, Kok-Seong ;

Dedon, Peter ;

Wernig, Marius ;

Mullen, Alan C. ;

Xing, Yi ;

Giallourakis, Cosmas C. ;

Chang, Howard Y. .

CELL STEM CELL, 2014, 15 (06) :707-719

[4] Notch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem Cells [J].

Bjornson, Christopher R. R. ;

Cheung, Tom H. ;

Liu, Ling ;

Tripathi, Pinky V. ;

Steeper, Katherine M. ;

Rando, Thomas A. .

STEM CELLS, 2012, 30 (02) :232-242

[5] A temporal switch from Notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis [J].

Brack, Andrew S. ;

Conboy, Irina M. ;

Conboy, Michael J. ;

Shen, Jeanne ;

Rando, Thomas A. .

CELL STEM CELL, 2008, 2 (01) :50-59

[6] Regulation of skeletal myogenesis by Notch [J].

Buas, Matthew F. ;

Kadesch, Tom .

EXPERIMENTAL CELL RESEARCH, 2010, 316 (18) :3028-3033

[7] m6A RNA Methylation Is Regulated by MicroRNAs and Promotes Reprogramming to Pluripotency [J].

Chen, Tong ;

Hao, Ya-Juan ;

Zhang, Ying ;

Li, Miao-Miao ;

Wang, Meng ;

Han, Weifang ;

Wu, Yongsheng ;

Lv, Ying ;

Hao, Jie ;

Wang, Libin ;

Li, Ang ;

Yang, Ying ;

Jin, Kang-Xuan ;

Zhao, Xu ;

Li, Yuhuan ;

Ping, Xiao-Li ;

Lai, Wei-Yi ;

Wu, Li-Gang ;

Jiang, Guibin ;

Wang, Hai-Lin ;

Sang, Lisi ;

Wang, Xiu-Jie ;

Yang, Yun-Gui ;

Zhou, Qi .

CELL STEM CELL, 2015, 16 (03) :289-301

[8] The regulation of notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis [J].

Conboy, IM ;

Rando, TA .

DEVELOPMENTAL CELL, 2002, 3 (03) :397-409

[9] Notch-mediated restoration of regenerative potential to aged muscle [J].

Conboy, IM ;

Conboy, MJ ;

Smythe, GM ;

Rando, TA .

SCIENCE, 2003, 302 (5650) :1575-1577

[10] Transcriptome-wide mapping of N6-methyladenosine by m6A-seq based on immunocapturing and massively parallel sequencing [J].

Dominissini, Dan ;

Moshitch-Moshkovitz, Sharon ;

Salmon-Divon, Mali ;

Amariglio, Ninette ;

Rechavi, Gideon .

NATURE PROTOCOLS, 2013, 8 (01) :176-189

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