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Muscle-secreted granulocyte colony-stimulating factor functions as metabolic niche factor ameliorating loss of muscle stem cells in aged mice.
The EMBO Journal ( IF 9.4 ) Pub Date : 2019-11-18 , DOI: 10.15252/embj.2019102154 Hu Li 1 , Qian Chen 1 , Changyin Li 1 , Ran Zhong 1 , Yixia Zhao 1 , Qianying Zhang 1 , Weimin Tong 2, 3 , Dahai Zhu 1, 4 , Yong Zhang 1
The EMBO Journal ( IF 9.4 ) Pub Date : 2019-11-18 , DOI: 10.15252/embj.2019102154 Hu Li 1 , Qian Chen 1 , Changyin Li 1 , Ran Zhong 1 , Yixia Zhao 1 , Qianying Zhang 1 , Weimin Tong 2, 3 , Dahai Zhu 1, 4 , Yong Zhang 1
Affiliation
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The function and number of muscle stem cells (satellite cells, SCs) decline with muscle aging. Although SCs are heterogeneous and different subpopulations have been identified, it remains unknown whether a specific subpopulation of muscle SCs selectively decreases during aging. Here, we find that the number of SCs expressing high level of transcription factor Pax7 (Pax7Hi ) is dramatically reduced in aged mice. Myofiber-secreted granulocyte colony-stimulating factor (G-CSF) regulates age-dependent loss of Pax7Hi cells, as the Pax7Hi SCs are replenished by exercise-induced G-CSF in aged mice. Mechanistically, we show that transcription of G-CSF (Csf3) gene in myofibers is regulated by MyoD in a metabolism-dependent manner. Furthermore, myofiber-secreted G-CSF acts as a metabolic niche factor required for establishing and maintaining the Pax7Hi SC subpopulation in adult and physiological aged mice by promoting the asymmetric division of Pax7Hi and Pax7Mi SCs. Together, our findings uncover that muscles provide a metabolic niche regulating Pax7 SC heterogeneity in mice.
中文翻译：
肌肉分泌的粒细胞集落刺激因子起代谢利基因子的作用，可改善衰老小鼠肌肉干细胞的损失。
肌肉干细胞（卫星细胞，SC）的功能和数量随着肌肉衰老而下降。尽管SCs是异质的，并且已鉴定出不同的亚群，但尚不清楚肌肉SCs的特定亚群在衰老过程中是否选择性降低。在这里，我们发现，在老年小鼠中，表达高水平转录因子Pax7（Pax7Hi）的SC数量显着减少。肌纤维分泌的粒细胞集落刺激因子（G-CSF）调节了Pax7Hi细胞的年龄依赖性丧失，因为Pax7Hi SCs通过运动诱导的G-CSF在老年小鼠中得到补充。从机制上讲，我们表明肌纤维中G-CSF（Csf3）基因的转录受MyoD代谢依赖方式的调节。此外，肌纤维分泌的G-CSF通过促进Pax7Hi和Pax7Mi SC的不对称分裂，是在成年和生理性衰老小鼠中建立和维持Pax7Hi SC亚群所需的代谢性利基因子。在一起，我们的发现揭示了肌肉在小鼠中提供了调节Pax7 SC异质性的代谢位。
更新日期：2019-12-17
中文翻译：
肌肉分泌的粒细胞集落刺激因子起代谢利基因子的作用，可改善衰老小鼠肌肉干细胞的损失。
肌肉干细胞（卫星细胞，SC）的功能和数量随着肌肉衰老而下降。尽管SCs是异质的，并且已鉴定出不同的亚群，但尚不清楚肌肉SCs的特定亚群在衰老过程中是否选择性降低。在这里，我们发现，在老年小鼠中，表达高水平转录因子Pax7（Pax7Hi）的SC数量显着减少。肌纤维分泌的粒细胞集落刺激因子（G-CSF）调节了Pax7Hi细胞的年龄依赖性丧失，因为Pax7Hi SCs通过运动诱导的G-CSF在老年小鼠中得到补充。从机制上讲，我们表明肌纤维中G-CSF（Csf3）基因的转录受MyoD代谢依赖方式的调节。此外，肌纤维分泌的G-CSF通过促进Pax7Hi和Pax7Mi SC的不对称分裂，是在成年和生理性衰老小鼠中建立和维持Pax7Hi SC亚群所需的代谢性利基因子。在一起，我们的发现揭示了肌肉在小鼠中提供了调节Pax7 SC异质性的代谢位。
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