Disturbance of calcium homeostasis and myogenesis caused by TET2 deletion in muscle stem cells

Haoyuan Zhang; Sheng Wang; Qiangwei Zhou; Yinlong Liao; Wenzhe Luo; Zhelun Peng; Ruimin Ren; Heng Wang

doi:10.1038/s41420-022-01041-1

Disturbance of calcium homeostasis and myogenesis caused by TET2 deletion in muscle stem cells

Cell Death Discov. 2022 Apr 30;8(1):236. doi: 10.1038/s41420-022-01041-1.

Authors

Haoyuan Zhang¹, Sheng Wang¹, Qiangwei Zhou², Yinlong Liao¹, Wenzhe Luo¹, Zhelun Peng¹, Ruimin Ren¹, Heng Wang³

Affiliations

¹ Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
² Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, China.
³ Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China. wangheng@mail.hzau.edu.cn.

Abstract

Skeletal muscle myogenesis is a sophisticated process controlled by genetic and epigenetic regulators. In animals, one of the key enzymes for the DNA demethylation of 5-methylcytosine is TET2. Although TET2 is essential for muscle development, the mechanisms by which TET2 regulates myogenesis, particularly the implication for muscle stem cells, remains unclear. In the present study, we employed the TET2 knockout mouse model to investigate the function of TET2 in muscle development and regeneration. We observed that TET2 deficiency caused impaired muscle stem cell proliferation and differentiation, resulting in the reduction in both myofiber number and muscle tissue size. Specifically, TET2 maintains calcium homeostasis in muscle stem cells by controlling the DNA methylation levels of the calcium pathway genes. Forced expression of the sodium/calcium exchanger protein SLC8A3 could rescue the myogenic defects in TET2 knockout cells. Our data not only illustrated the vital function of TET2 during myogenesis but also identified novel targets that contribute to calcium homeostasis for enhancing muscle function.