Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, 225 South Chongqing Road, Shanghai 200025, China.
Stem Cell Res Ther. 2010 Dec 14;1(5):39. doi: 10.1186/scrt39.
Pluripotency, a characteristic of cells in the inner cell mass of the mammalian preimplantation blastocyst as well as of embryonic stem cells, is defined as the ability of a cell to generate all of the cell types of an organism. A group of transcription factors is essential for the establishment and maintenance of the pluripotent state. Recent studies have demonstrated that differentiated somatic cells could be reverted to a pluripotent state by the overexpression of a set of transcription factors, further highlighting the significance of transcription factors in the control of pluripotency. Among these factors, a member of the POU transcription factor family, Oct4, is central to the machinery governing pluripotency. Oct4 is highly expressed in pluripotent cells and becomes silenced upon differentiation. Interestingly, the precise expression level of Oct4 determines the fate of embryonic stem cells. Therefore, to control the expression of Oct4 precisely, a variety of regulators function at multiple levels, including transcription, translation of mRNA and post-translational modification. Additionally, in cooperation with Sox2, Nanog and other members of the core transcriptional regulatory circuitry, Oct4 activates both protein-coding genes and noncoding RNAs necessary for pluripotency. Simultaneously, in association with transcriptional repressive complexes, Oct4 represses another set of targets involved in developmental processes. Importantly, Oct4 can re-establish pluripotency in somatic cells, and proper reprogramming of Oct4 expression is indispensable for deriving genuine induced pluripotent stem cell lines. In the past several years, genome-wide identification of Oct4 target genes and Oct4-centered protein interactomes has been reported, indicating that Oct4 exerts tight control over pluripotency regulator expression and protects embryonic stem cells in an undifferentiated state. Nevertheless, further investigation is required to fully elucidate the underlying molecular mechanisms through which Oct4 maintains and reinitiates pluripotency. Systemic and dynamic exploration of the protein complexes and target genes associated with Oct4 will help to elucidate the role of Oct4 more comprehensively.
多能性是哺乳动物着床前胚胎囊胚内细胞团以及胚胎干细胞的特征，它是指一个细胞产生一个生物体所有细胞类型的能力。一组转录因子对于建立和维持多能状态是必不可少的。最近的研究表明，通过过度表达一组转录因子，分化的体细胞核可以被重编程为多能状态，这进一步强调了转录因子在控制多能性中的重要性。在这些因子中，POU 转录因子家族的一个成员 Oct4 是调控多能性的核心机制。Oct4 在多能细胞中高度表达，在分化时沉默。有趣的是，Oct4 的精确表达水平决定了胚胎干细胞的命运。因此，为了精确控制 Oct4 的表达，各种调节剂在多个水平上发挥作用，包括转录、mRNA 翻译和翻译后修饰。此外，Oct4 与 Sox2、Nanog 和其他核心转录调控回路成员合作，激活维持多能性所必需的蛋白质编码基因和非编码 RNA。同时，与转录抑制复合物结合，Oct4 抑制另一组涉及发育过程的靶基因。重要的是，Oct4 可以在体细胞中重新建立多能性，并且正确地重新编程 Oct4 的表达对于获得真正的诱导多能干细胞系是必不可少的。在过去的几年中，已经报道了全基因组鉴定的 Oct4 靶基因和以 Oct4 为中心的蛋白质相互作用组，表明 Oct4 对多能性调控因子的表达进行严格控制，并使胚胎干细胞保持未分化状态。然而，需要进一步研究以充分阐明 Oct4 维持和重新启动多能性的潜在分子机制。系统地和动态地探索与 Oct4 相关的蛋白质复合物和靶基因将有助于更全面地阐明 Oct4 的作用。
