Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Exp Mol Med. 2017 Nov 24;49(11):e401. doi: 10.1038/emm.2017.191.
Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells is unknown. In the present study, we elucidated the importance of Trib2 in maintaining pluripotency in mouse ES cells and in generating iPS cells from somatic cells through the reprogramming process. Trib2 expression decreased as ES cells differentiated, and Trib2 knockdown in ES cells changed their colony morphology while reducing the activity of alkaline phosphatase and the expression of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4. Trib2 directly interacted with Oct4 and elevated Oct4 promoter activity. During the generation of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse embryonic fibroblasts, whereas Trib2 overexpression significantly increased their reprogramming efficiency. In summary, our results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process.
胚胎干细胞（ES 细胞）是具有自我更新能力和分化潜能的多能细胞。诱导多能干细胞（iPS 细胞）是通过引入核心重编程因子从体细胞中获得的与 ES 细胞等效的细胞。ES 和 iPS 细胞是理解基础生物学和生成用于临床应用的治疗细胞的重要来源。Tribbles 同源物 2（Trib2）作为信号通路中的支架发挥作用。然而，Trib2 与 ES 和 iPS 细胞的多能性的相关性尚不清楚。在本研究中，我们通过重编程过程阐明了 Trib2 在维持小鼠 ES 细胞多能性和从体细胞生成 iPS 细胞中的重要性。随着 ES 细胞分化，Trib2 的表达减少，Trib2 在 ES 细胞中的敲低改变了它们的集落形态，同时降低碱性磷酸酶的活性和多能性标记基因 Oct4、Sox2、Nanog 和 Klf4 的表达。Trib2 与 Oct4 直接相互作用，并提高 Oct4 启动子活性。在 iPS 细胞的生成过程中，Trib2 的敲低降低了小鼠胚胎成纤维细胞的重编程效率，而 Trib2 的过表达则显著提高了其重编程效率。总之，我们的结果表明 Trib2 对于维持 ES 细胞的自我更新和在重编程过程中诱导多能性很重要。
