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Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control

Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolit...

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Published in:Cell discovery 2024-09, Vol.10 (1), p.94-19, Article 94
Main Authors: Zhang, Qianying, Han, Wanhong, Wu, Rimao, Deng, Shixian, Meng, Jiemiao, Yang, Yuanping, Li, Lili, Sun, Mingwei, Ai, Heng, Chen, Yingxi, Liu, Qinyao, Gao, Tian, Niu, Xingchen, Liu, Haixia, Zhang, Li, Zhang, Dan, Chen, Meihong, Yin, Pengbin, Zhang, Licheng, Tang, Peifu, Zhu, Dahai, Zhang, Yong, Li, Hu
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container_title Cell discovery
container_volume 10
creator Zhang, Qianying
Han, Wanhong
Wu, Rimao
Deng, Shixian
Meng, Jiemiao
Yang, Yuanping
Li, Lili
Sun, Mingwei
Ai, Heng
Chen, Yingxi
Liu, Qinyao
Gao, Tian
Niu, Xingchen
Liu, Haixia
Zhang, Li
Zhang, Dan
Chen, Meihong
Yin, Pengbin
Zhang, Licheng
Tang, Peifu
Zhu, Dahai
Zhang, Yong
Li, Hu
description Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A -knockout (KO) and Myod -KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.
doi_str_mv 10.1038/s41421-024-00712-w
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subjects 631/337/574
631/532/2439
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Cycle Analysis
Cell Physiology
Life Sciences
Stem Cells
title Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control
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