PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress.
PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress.
复制标题
PAX3 赋予骨骼肌干细胞对环境压力反应的功能异质性。
DOI：
10.1016/j.stem.2019.03.019
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发表时间：
2019
期刊：
影响因子：
23.9
通讯作者：
Relaix,Frédé
中科院分区：
文献类型：
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作者：
DerVartanian,Audrey;Quétin,Marie;Michineau,Stéphanie;Auradé,Frédéric;Hayashi,Shinichiro;Dubois,Christelle;Rocancourt,Didier;Drayton-Libotte,Bernadette;Szegedi,Anikó;Buckingham,Margaret;Conway,SimonJ;Gervais,Marianne;Relaix,Frédé
肌肉卫星细胞（Muscle Satellite Cells，MuSC）是成体骨骼肌修复所需的静止期肌肉干细胞。环境压力，如污染对MuSC行为的影响仍然是未知的。我们通过结合小鼠体内分子遗传学模型和体内研究评估了2，3，7，8-四氯二苯并对二恶英（TCDD）暴露对MuSCs的影响。虽然所有的MuSC都表达转录因子PAX 7，但我们发现一个子集也表达PAX 3并表现出对环境胁迫的抵抗力。在全身性TCDD治疗后，PAX 3阴性MuSC通过外源性芳烃受体信号传导显示受损的存活、非典型活化和散发性分化。我们进一步表明，PAX 3阳性的MuSCs变得敏感的环境压力时，PAX 3功能受损，PAX 3介导的诱导mTORC 1的保护是必需的。因此，我们的研究确定了MuSCs在响应PAX 3控制的环境应激时的功能异质性。
Muscle satellite cells (MuSCs) are the quiescent muscle stem cells required for adult skeletal muscle repair. The impact of environmental stress such as pollution on MuSC behavior remains unexplored. We evaluated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, a ubiquitous and highly toxic pollutant, on MuSCs by combiningin vivomouse molecular genetic models withex vivostudies. While all MuSCs express the transcription factor PAX7, we show that a subset also express PAX3 and exhibit resistance to environmental stress. Upon systemic TCDD treatment, PAX3-negative MuSCs display impaired survival, atypical activation, and sporadic differentiation through xenobiotic aryl hydrocarbon receptor signaling. We further show that PAX3-positive MuSCs become sensitized to environmental stress when PAX3 function is impaired and that PAX3-mediated induction of mTORC1 is required for protection. Our study, therefore, identifies a functional heterogeneity of MuSCs in response to environmental stress controlled by PAX3.