Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle

eLife

Yusei Takemoto¹  Akihiro Kaneshige¹  Lidan Zhang²  So-ichiro Fukada²  Akihito Harada²  Akiyoshi Uezumi²  Takayuki Kaji²  Yu-taro Noguchi³  Yasuyuki Ohkawa³  Kazutake Tsujikawa³  Kazumitsu Maehara³  Hiroki Kokubo³  Sumiaki Fukuda³ 

[1] Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc, Takatsuki, Japan;Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan;Project for Muscle Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan;

关键词: skeletal muscle;    satellite cells;    hypertrophy;    Notch;   

DOI  :  10.7554/eLife.48284

来源: DOAJ

【 摘 要 】

In overloaded and regenerating muscle, the generation of new myonuclei depends on muscle satellite cells (MuSCs). Because MuSC behaviors in these two environments have not been considered separately, MuSC behaviors in overloaded muscle remain unexamined. Here, we show that most MuSCs in overloaded muscle, unlike MuSCs in regenerating muscle, proliferate in the absence of MyoD expression. Mechanistically, MuSCs in overloaded muscle sustain the expression of Heyl, a Notch effector gene, to suppress MyoD expression, which allows effective MuSC proliferation on myofibers and beneath the basal lamina. Although Heyl-knockout mice show no impairment in an injury model, in a hypertrophy model, their muscles harbor fewer new MuSC-derived myonuclei due to increased MyoD expression and diminished proliferation, which ultimately causes blunted hypertrophy. Our results show that sustained HeyL expression is critical for MuSC proliferation specifically in overloaded muscle, and thus indicate that the MuSC-proliferation mechanism differs in overloaded and regenerating muscle.

【 授权许可】

Unknown