Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle
| Autor: | Akihiro Kaneshige, Yasuyuki Ohkawa, Akiyoshi Uezumi, Lidan Zhang, So-ichiro Fukada, Yusei Takemoto, Kazutake Tsujikawa, Yu Taro Noguchi, Takayuki Kaji, Akihito Harada, Sumiaki Fukuda, Kazumitsu Maehara, Hiroki Kokubo |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Notch Mouse Satellite Cells Skeletal Muscle QH301-705.5 Science Biology MyoD Regenerative medicine General Biochemistry Genetics and Molecular Biology Muscle hypertrophy Mice 03 medical and health sciences 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors medicine Animals Regeneration skeletal muscle Biology (General) Cell Proliferation MyoD Protein Mice Knockout satellite cells General Immunology and Microbiology Effector Muscles General Neuroscience Skeletal muscle General Medicine musculoskeletal system Stem Cells and Regenerative Medicine Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Medicine Basal lamina Injury model Stem cell hypertrophy 030217 neurology & neurosurgery Research Article |
| Zdroj: | eLife, Vol 8 (2019) eLife |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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