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.
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