The status of a cell, at which it appears to loose its proliferating capacity, is termed as "senescence". It is well accepted that cellular senescence is a result of changes in gene expression and or epigenetic modifications. For example, histone deacetylase inhibitors, which decondense chromatin and stimulate the transcription of some genes, can induce senescence- like state in human fibroblasts (Ogryzko et al., 1996). Other studies show that senescence is associated with subtle changes in the nuclear morphology and formation of a distinct chromatin structure, called senescence-associated hetero-chromatic foci (SAHF) (Narita et al., 2003). However, the most fundamental property of ESCs is that they can self renew indefinitely in culture (Thomson et al., 1998; Carpenter et al., 2004; Rosler et al., 2004). We have also been successfully growing our cell line, ReliCell®hES1 (Mandal et al.,
2006), over more than 60 passages which is equivalent to have undergone about 200 population doublings, without having developed any alterations in terms of genomic and epigenomic stability (Pal et al., 2007). Reports suggest that the capacity of hESCs to bypass senescence is not due to acquisition of genotypic abnormalities in long term propagation (Brimble et al., 2004). Furthermore, detailed single nucleotide polymorphism (SNP) analysis and mitochondrial DNA sequencing has demonstrated an overall remarkable stability of hESC (Maitra et al., 2005). It emerges therefore, that the lack of normal senescence in ESC is neither transient nor sporadic, but is truly inherent. Hence, it is understandable that there will be several factors which function in an organized fashion to maintain the self renewal capacity of the ESCs. Key differences in cell cycle control, regulation of telomerase expression and DNA repair has been identified by gene expression profiling of both mESCs and hESCs (Miura et al., 2004b; Ginis et al., 2004).
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