miR-378-mediated glycolytic metabolism enriches the Pax7(Hi) subpopulation of satellite cells.
miR-378-mediated glycolytic metabolism enriches the Pax7(Hi) subpopulation of satellite cells.
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miR-378介导的糖酵解代谢丰富了卫星细胞的Pax7Hi亚群
DOI：
10.1186/s13619-022-00112-z
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发表时间：
2022-04-02
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Li H;Kang L;Wu R;Li C;Zhang Q;Zhong R;Jia L;Zhu D;Zhang Y
成体骨骼肌干细胞，也称为卫星细胞（SC），是一个高度异质性的群体，并驻留在基膜和肌纤维肌膜之间。肌纤维作为一个直接的生态位，以支持SC自我更新和肌肉生长和再生过程中的激活。在此，我们证明了microRNA 378（miR-378）调节骨骼肌纤维中的糖酵解代谢，如通过肌纤维特异性miR-378转基因小鼠（TG）的分析所证明的。随后，我们使用miR-378 TG小鼠评估SC功能和肌肉再生。我们证明，由于SC的激活和分化延迟，miR-378 TG小鼠显着减弱了肌肉再生。此外，我们表明miR-378介导的代谢开关富集Pax 7 HiSC，解释了miR-378 TG小鼠中受损的肌肉再生。从机制上讲，我们的数据表明，miR-378靶向Akt 1/FoxO 1通路，这有助于miR-378 TG小鼠中Pax 7 HiSC的富集。总之，我们的研究结果表明，miR-378是将纤维代谢与肌肉干细胞异质性联系起来的靶点，并提供了一个遗传模型来证实肌纤维在调节肌肉干细胞行为和功能中的代谢生态位作用。
Adult skeletal muscle stem cells, also known satellite cells (SCs), are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma. Myofibers function as an immediate niche to support SC self-renewal and activation during muscle growth and regeneration. Herein, we demonstrate that microRNA 378 (miR-378) regulates glycolytic metabolism in skeletal muscle fibers, as evidenced by analysis of myofiber-specific miR-378 transgenic mice (TG). Subsequently, we evaluate SC function and muscle regeneration using miR-378 TG mice. We demonstrate that miR-378 TG mice significantly attenuate muscle regeneration because of the delayed activation and differentiation of SCs. Furthermore, we show that the miR-378-mediated metabolic switch enriches Pax7HiSCs, accounting for impaired muscle regeneration in miR-378 TG mice. Mechanistically, our data suggest that miR-378 targets the Akt1/FoxO1 pathway, which contributes the enrichment of Pax7HiSCs in miR-378 TG mice. Together, our findings indicate that miR-378 is a target that links fiber metabolism to muscle stem cell heterogeneity and provide a genetic model to approve the metabolic niche role of myofibers in regulating muscle stem cell behavior and function.