Su Yixun, Zhang Wenjun, Patro C Pawan K, Zhao Jing, Mu Tianhao, Ma Zhongnan, Xu Jianqiang, Ban Kenneth, Yi Chenju, Zhou Yi
The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Cell Dev Biol. 2020 May 19;8:362. doi: 10.3389/fcell.2020.00362. eCollection 2020.
The proliferation and differentiation of neural progenitor lay the foundation for brain development. In neural progenitors, activation of Signal Transducer and Activator of Transcription 3 (STAT3) has been found to promote proliferation and astrocytogenesis while suppressing neurogenesis. However, our study found that conditional knockout in neural progenitors ( cKO) also results in increased proliferation and suppressed neurogenesis. To investigate how STAT3 regulates these processes, we attempted to identify potential STAT3 target genes by RNA-seq profiling of the control (CTL) and cKO neural progenitors. We found that STAT3 promotes the expression of genes involved in the mitochondrial oxidative phosphorylation (OXPHOS), and thereby promotes mitochondrial respiration and negatively regulates reactive oxygen species (ROS) production. In addition, we demonstrated that loss-of-function promotes proliferation via regulation of mitochondrial metabolism and downstream signaling pathways. Our study provides novel insights into the relation between STAT3, mitochondrial metabolism and the process of embryonic neurogenesis.
神经祖细胞的增殖和分化为大脑发育奠定了基础。在神经祖细胞中，已发现信号转导子和转录激活子3（STAT3）的激活可促进增殖和星形胶质细胞生成，同时抑制神经发生。然而，我们的研究发现，神经祖细胞中的条件性敲除（cKO）也会导致增殖增加和神经发生受到抑制。为了研究STAT3如何调节这些过程，我们试图通过对照（CTL）和cKO神经祖细胞的RNA测序分析来鉴定潜在的STAT3靶基因。我们发现STAT3促进参与线粒体氧化磷酸化（OXPHOS）的基因表达，从而促进线粒体呼吸并负向调节活性氧（ROS）的产生。此外，我们证明功能丧失通过调节线粒体代谢和下游信号通路促进增殖。我们的研究为STAT3、线粒体代谢与胚胎神经发生过程之间的关系提供了新的见解。
