法国巴黎大学医学院Frédéric Relaix研究组近日取得一项新成果。他们探明了骨骼肌干细胞受到环境污染物胁迫后，通过PAX3诱导mTORC1表达进行功能异质性调控，以保护骨骼肌免受毒害。 2019年6月，国际知名学术期刊《Cell Stem Cell》发表了这一成果。

该研究组结合小鼠体内分子遗传模型和体外研究，评估了普遍存在的剧毒污染物2，3，7，8四氯二苯并对二恶英（TCDD）暴露对肌肉的影响。当所有的肌肉都表达转录因子PAX7时，研究人员发现，一个同时表达PAX3的亚单位对环境压力表现出抵抗力。经系统性TCDD治疗后，PAX3阴性肌肉通过外源性芳基烃受体信号显示生存受损、非典型激活和散发性分化。课题组进一步证明，当PAX3功能受损时，PAX3阳性的肌肉对环境压力敏感，并且需要PAX3诱导的mTORC1表达。因此，研究确定了PAX3在骨骼肌干细胞对环境应激反应中的功能异质性调控。

研究人员表示，骨骼肌卫星细胞(MuSCs)是成年骨骼肌修复所必需的静态肌干细胞。环境压力(如污染)对MuSC行为的影响尚待探索。

附：英文原文

Title: PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress

Author: Audrey Der Vartanian, Marie Quétin, Stéphanie Michineau, Simon J. Conway, Marianne Gervais, Frédéric Relaix|Inserm, IMRB U-E, Créteil, France,

Issue&Volume:Jun 06, 2019 Volume 24Issue 6

Abstract: 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 combining in vivo mouse molecular genetic models with ex vivo studies. 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.

DOI: https://doi.org/10.1016/j.stem.2019.03.019

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30118-3