Stem Cell Institute, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Histol Histopathol. 2010 Mar;25(3):405-12. doi: 10.14670/HH-25.405.
Oct4 is one of the most important transcription factors required to maintain an undifferentiated state (self-renewal) and pluripotency of human and mouse embryonic stem (ES) cells as well as early embryonic cells. In addition, Oct4 is the only known transcription factor that has to be exogenously introduced into differentiated cells to make induced pluripotent stem (iPS) cells. Therefore, it is of great importance to understand how Oct4 transcription is regulated in ES cells and embryos and how it becomes activated during iPS cell formation. In this article, we will review the regulation of the mouse Oct4 gene from the viewpoint of DNA methylation, binding of orphan nuclear receptors, histone modifications and synergistic effects with other pluripotency factors. We will also raise several key questions that need to be addressed in future work to improve our understanding of Oct4 gene regulation and its essential role in self-renewal and pluripotency.
Oct4 是维持人类和小鼠胚胎干细胞(ES 细胞)以及早期胚胎细胞未分化状态(自我更新)和多能性所必需的最重要的转录因子之一。此外,Oct4 是唯一已知的转录因子,必须外源性引入分化细胞中才能产生诱导多能干细胞(iPS 细胞)。因此,了解 ES 细胞和胚胎中 Oct4 转录如何被调控以及在 iPS 细胞形成过程中如何被激活是非常重要的。在本文中,我们将从 DNA 甲基化、孤儿核受体结合、组蛋白修饰以及与其他多能性因子的协同作用的角度来综述 Oct4 基因在小鼠中的调控。我们还将提出几个需要在未来工作中解决的关键问题,以提高我们对 Oct4 基因调控及其在自我更新和多能性中的重要作用的理解。