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Mdfi Promotes C2C12 Cell Differentiation and Positively Modulates Fast-to-Slow-Twitch Muscle Fiber Transformation

文献类型： 外文期刊

作者： Huang, Bo 1 ; Jiao, Yiren 1 ; Zhu, Yifan 1 ; Ning, Zuocheng 1 ; Ye, Zijian 1 ; Li, Qing X. 2 ; Hu, Chingyuan 3 ; Wang, Ch 1 ;

作者机构： 1.South China Agr Univ, Natl Engn Res Ctr Breeding Swine Ind, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Guangdong Lab Lingnan Modem Agr,Coll Anim Sci, Guangzhou, Peoples R China

2.Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA

3.Univ Hawaii Manoa, Dept Human Nutr Food & Anim Sci, Honolulu, HI 96822 USA

关键词： Mdfi; CRISPR; Cas9 system; RNA-seq; differentiation; muscle fiber type transformation

期刊名称：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY （ 影响因子：6.684； 五年影响因子：7.219 ）

ISSN： 2296-634X

年卷期： 2021 年 9 卷

页码：

收录情况： SCI

摘要： Muscle development requires myoblast differentiation and muscle fiber formation. Myod family inhibitor (Mdfi) inhibits myogenic regulatory factors in NIH3T3 cells, but how Mdfi regulates myoblast myogenic development is still unclear. In the present study, we constructed an Mdfi-overexpression (Mdfi-OE) C2C12 cell line by the CRISPR/Cas9 system and performed RNA-seq on Mdfi-OE and wild-type (WT) C2C12 cells. The RNA-seq results showed that the calcium signaling pathway was the most significant. We also established the regulatory networks of Mdfi-OE on C2C12 cell differentiation and muscle fiber type transformation and identified hub genes. Further, both RNA-seq and experimental verification demonstrated that Mdfi promoted C2C12 cell differentiation by upregulating the expression of Myod, Myog, and Myosin. We also found that the positive regulation of Mdfi on fast-to-slow-twitch muscle fiber transformation is mediated by Myod, Camk2b, and its downstream genes, such as Pgc1a, Pdk4, Cs, Cox4, Acadm, Acox1, Cycs, and Atp5a1. In conclusion, our results demonstrated that Mdfi promotes C2C12 cell differentiation and positively modulates fast-to-slow-twitch muscle fiber transformation. These findings further our understanding of the regulatory mechanisms of Mdfi in myogenic development and muscle fiber type transformation. Our results suggest potential therapeutic targets for muscle- and metabolic-related diseases.

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