Open AccessMRTF‐A regulates myoblast commitment to differentiation by targeting PAX7 during muscle regeneration
Author(s) -
Song Ruhui,
Zhao Shengnan,
Xu Yue,
Hu Jian,
Ke Shuangao,
Li Fan,
Tian Gaohui,
Zheng Xiao,
Li Jiajun,
Gu Lixing,
Xu Yao
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16820
Subject(s) - myod , c2c12 , myocyte , gene knockdown , microbiology and biotechnology , biology , myod protein , transcription factor , regeneration (biology) , myocardin , myogenin , skeletal muscle , cellular differentiation , stem cell , myogenesis , serum response factor , endocrinology , cell culture , genetics , gene
Myocardin‐related transcription factor‐A/serum response factor (MRTF‐A/SRF), a well‐known transcriptional programme, has been proposed to play crucial roles in skeletal muscle development and function. However, whether MRTF‐A participates in muscle regeneration and the molecular mechanisms are not completely understood. Here, we show that MRTF‐A levels are highly correlated with myogenic genes using a RNA‐seq assay, which reveal that MRTF‐A knockdown in C2C12 cells significantly reduces PAX7 expression. Subsequent in vitro and in vivo data show that MRTF‐A and PAX7 present identical expression patterns during myoblast differentiation and CTX‐induced muscle injury and repair. Remarkably, MRTF‐A overexpression promotes myoblast proliferation, while inhibiting cell differentiation and the expression of MyoD and MyoG. MRTF‐A loss of function produces the opposite effect. Moreover, mice with lentivirus (MRTF‐A) injection possesses more PAX7 + satellite cells, but less differentiating MyoD + and MyoG + cells, leading subsequently to diminished muscle regeneration. Our mechanistic results reveal that MRTF‐A contributes to PAX7‐mediated myoblast self‐renewal, proliferation, and differentiation by binding to its distal CArG box. Overall, we propose that MRTF‐A functions as a novel PAX7 regulator upon myoblast commitment to differentiation, which could provide pathways for dictating muscle stem cell fate and open new avenues to explore stem cell‐based therapy for muscle degenerative diseases.