Since the discovery of so-called Yamanaka factors in 2006[4], a variety of different types of adult human somatic cells were experimentally converted into so-called induced pluripotent stem cells (iPSCs) in many respects resembling hESCs. Recent advances in application of somatic

compound library cancer cell nuclear transfer technology (SCNT) to human cells led to breakthroughs in producing human pluripotent stem cells almost indistinguishable from hESCs[5,6]. Arguably, the most studied among different types of human pluripotent stem cells are hESCs. These cells readily demonstrate a stable developmental potential to form derivatives of all three embryonic germ layers, and can be

kept in the undifferentiated state in culture for prolonged periods, if not indefinitely. Human pluripotent stem cells are promising candidates for development of novel models to study human developmental biology, to promote drug discovery, and to foster efforts for cell-based regenerative medicine. To realize the potential of hESCs in practice would require growing and expansion of these cells in culture, during which hESCs may face many challenges. For example, hESCs experience culture stress, and stress associated with genotoxic agents, ubiquitous in nature. In real life situations, exposures to electromagnetic ionizing radiation (IR) stemming from cosmic rays, natural background radioactive isotopes, and

many other sources are inevitable. Many studies indicate IR as being one of the most potent cytotoxic and genotoxic agents[7,8]. One of the key manifestations of the biological effects of IR is the change in global gene expression, which may dictate the ultimate hESCs fate after genotoxic stress. Detailed analyses of the available evidence of alterations in gene expression in human pluripotent stem cells after IR exposures will help pave the way for future research and strategical planning in this important area of studies. GENE EXPRESSION-SPECIFIC SIGNATURE OF HESCS The global gene expression signature of hESCs has been examined by many modern assays, including serial analysis Dacomitinib of gene expression (SAGE), DNA microarray analysis, and new-generation, massively parallel signature sequencing (NGS). As a result of these studies, some key genes that regulate pluripotency and self-renewal, were identified and verified as being expressed in all lines of undifferentiated hESCs, such as POU5F1, SOX2, NANOG, and several others[9-11]. A remarkable heterogeneity and variability in gene expression was found in many functional classes of genes across multiple lines of hESCs, including but not limited to housekeeping genes, and some “stemness” genes, such as STAT3 and RUNX1[12].