Epigenetic Instability in Embryonic Stem Cells

Embryonic stem (ES) cells constitute a very important tool for regenerative medicine today. Human ES cells, in particular, are almost all derived from embryos obtained by in vitro fer‐ tilization (IVF) followed by in vitro culture (IVC); however, such in vitro manipulated em‐ bryos often show epigenetic abnormalities in imprinted genes that can lead to the development of various diseases. We recently reported that epigenetic differences occurred between ES cells derived from in vivo developed embryos (Vivo ES) and ES cells derived from in vitro manipulated embryos (Vitro ES) [1]. In addition, we found that the DNA meth‐ ylation state of uniparental and somatic cell nuclear transfer (SCNT) ES cells exhibits epige‐ netic instability during in vitro culture [2]. In this chapter, we review studies that have examined the epigenetic instability of ES cells during generation and maintenance cultures, and discuss the candidate factors that may be responsible for this epigenetic instability.