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

Sumiaki Fukuda, Akihiro Kaneshige, Takayuki Kaji, Yu Taro Noguchi, Yusei Takemoto, Lidan Zhang, Kazutake Tsujikawa, Hiroki Kokubo, Akiyoshi Uezumi, Kazumitsu Maehara, Akihito Harada, Yasuyuki Ohkawa, So Ichiro Fukada

研究成果: ジャーナルへの寄稿記事

抄録

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 MuSCderived 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 MuSCproliferation mechanism differs in overloaded and regenerating muscle.

元の言語英語
記事番号e48284
ジャーナルeLife
8
DOI
出版物ステータス出版済み - 9 2019

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Stem cells
Muscle Cells
Muscle
Stem Cells
Muscles
Satellites
Hypertrophy
Cell Proliferation
Cell proliferation
Basement Membrane
Knockout Mice
Wounds and Injuries
Ports and harbors
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Fukuda, S., Kaneshige, A., Kaji, T., Noguchi, Y. T., Takemoto, Y., Zhang, L., ... Fukada, S. I. (2019). Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle. eLife, 8, [e48284]. https://doi.org/10.7554/eLife.48284

Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle. / Fukuda, Sumiaki; Kaneshige, Akihiro; Kaji, Takayuki; Noguchi, Yu Taro; Takemoto, Yusei; Zhang, Lidan; Tsujikawa, Kazutake; Kokubo, Hiroki; Uezumi, Akiyoshi; Maehara, Kazumitsu; Harada, Akihito; Ohkawa, Yasuyuki; Fukada, So Ichiro.

:: eLife, 巻 8, e48284, 09.2019.

研究成果: ジャーナルへの寄稿記事

Fukuda, S, Kaneshige, A, Kaji, T, Noguchi, YT, Takemoto, Y, Zhang, L, Tsujikawa, K, Kokubo, H, Uezumi, A, Maehara, K, Harada, A, Ohkawa, Y & Fukada, SI 2019, 'Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle', eLife, 巻. 8, e48284. https://doi.org/10.7554/eLife.48284
Fukuda S, Kaneshige A, Kaji T, Noguchi YT, Takemoto Y, Zhang L その他. Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle. eLife. 2019 9;8. e48284. https://doi.org/10.7554/eLife.48284
Fukuda, Sumiaki ; Kaneshige, Akihiro ; Kaji, Takayuki ; Noguchi, Yu Taro ; Takemoto, Yusei ; Zhang, Lidan ; Tsujikawa, Kazutake ; Kokubo, Hiroki ; Uezumi, Akiyoshi ; Maehara, Kazumitsu ; Harada, Akihito ; Ohkawa, Yasuyuki ; Fukada, So Ichiro. / Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle. :: eLife. 2019 ; 巻 8.
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abstract = "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 MuSCderived 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 MuSCproliferation mechanism differs in overloaded and regenerating muscle.",
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AU - Takemoto, Yusei

AU - Zhang, Lidan

AU - Tsujikawa, Kazutake

AU - Kokubo, Hiroki

AU - Uezumi, Akiyoshi

AU - Maehara, Kazumitsu

AU - Harada, Akihito

AU - Ohkawa, Yasuyuki

AU - Fukada, So Ichiro

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AB - 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 MuSCderived 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 MuSCproliferation mechanism differs in overloaded and regenerating muscle.

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