Mitochondrial metabolism and thyroid hormones: a game of influence over adult neural stem cell fate decision?

J. Gothié, Anthony Sébillot, C. Luongo, M. Legendre, Marine Perret-Jeanneret, K. L. Blay, S. Remaud, B. Demeneix
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Abstract

Unlike differentiated cells, stem cells use aerobic glycosylation rather than oxidative phosphorylation1. Moreover, metabolic status influences stem cell determination2. Thyroid hormones (THs) regulate neural stem cell (NSC) commitment towards a neuronal phenotype in adult brain3, but also have major roles in mitochondrial metabolism4. Given these complimentary roles, we investigated the convergence of THs and mitochondrial metabolism on NSC fate determination towards neuronal or glial fate. Following stereotaxic injection of the mitochondrial membrane potential marker (JC-1) into the adult mouse lateral ventricle, we observed greater mitochondrial activity in cells committed toward a neuronal than an oligodendroglial phenotype. Further, in vitro studies in neurospheres using a dye revealing ROS production (hydroethidine) show that THs increase ROS production and promote neuronal determination. These studies also showed that the activated form of DRP1 (pDRP1S616), mediating mitochondrial fission, is preferentially detected in the cytosol of neuronal lineage cells. Together, these results show that both THs and mitochondrial activity impact NSCs fate decision. We hypothesize that THs govern NSCs commitment through their effects on mitochondria. Future work will address the impact of modulating DRP1 expression in different thyroid contexts. This work should provide new insights into the mechanisms governing adult NSCs fate.
线粒体代谢和甲状腺激素:对成体神经干细胞命运决定的影响?
与分化的细胞不同,干细胞使用有氧糖基化而不是氧化磷酸化。此外,代谢状态影响干细胞的决定2。在成人大脑中,甲状腺激素(THs)调节神经干细胞(NSC)向神经元表型的承诺,但也在线粒体代谢中发挥重要作用。鉴于这些互补的作用,我们研究了THs和线粒体代谢在NSC命运决定神经元或胶质命运的收敛性。将线粒体膜电位标记物(JC-1)立体定向注射到成年小鼠侧脑室后,我们观察到神经元型细胞的线粒体活性高于少突胶质型细胞。此外,使用显示ROS生成的染料(氢乙啶)在神经球中的体外研究表明,这增加了ROS的生成并促进了神经元的测定。这些研究还表明,介导线粒体分裂的活化形式DRP1 (pDRP1S616)优先存在于神经元系细胞的细胞质中。总之,这些结果表明,THs和线粒体活性都会影响NSCs的命运决定。我们假设这通过对线粒体的影响来控制NSCs的承诺。未来的工作将探讨在不同甲状腺环境下调节DRP1表达的影响。这项工作应该为成人NSCs命运的机制提供新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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