Center for iPS Cell Research and Application, Kyoto University,Shogoin, Sakyo-ku, Kyoto, Japan.
Adv Genet. 2010;70:177-99. doi: 10.1016/B978-0-12-380866-0.60007-1.
Definition of stemness states that a stem cell population should be maintained over long periods of time, while generating all differentiated cell types of the corresponding tissues. Epigenetic regulation plays an important role in such process because the context of genome sequences is generally unchanged by differentiation process. Recent evidence indicates that an abnormal control of cellular differentiation is involved in the process of carcinogenesis [Hochedlinger, K., Yamada, Y., Beard, C., and Jaenisch, R. (2005). Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121, 465-477]. Therefore, understanding how cellular differentiation is controlled would be useful for obtaining a better understanding of the mechanisms underlying carcinogenesis. In this chapter, we will describe recent advances in understanding the epigenetic codes that govern differentiation of stem cells, especially focusing on embryonic stem cells. We will also discuss the concept of cancer stem cells, in which the epigenetic regulations control differentiation of tumor cells and such regulations play a central role in the determination of whether a tumor cell is capable of tumor initiation or not.
干性状态的定义是，干细胞群体应能长时间维持，同时生成相应组织的所有分化细胞类型。在这个过程中，表观遗传调控起着重要作用，因为基因组序列的上下文通常不会因分化过程而改变。最近的证据表明，细胞分化的异常控制参与了癌变过程[Hochedlinger, K., Yamada, Y., Beard, C., and Jaenisch, R. (2005). Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121, 465-477]。因此，了解细胞分化是如何被控制的，将有助于更好地理解癌变的机制。在本章中，我们将描述在理解控制干细胞分化的表观遗传密码方面的最新进展，特别是重点介绍胚胎干细胞。我们还将讨论癌症干细胞的概念，其中表观遗传调控控制肿瘤细胞的分化，这种调控在决定肿瘤细胞是否能够启动肿瘤方面起着核心作用。
