Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells.
Human pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth.
['Halliwell|Jason A|JA|', 'Frith|Thomas J R|TJR|', 'Laing|Owen|O|', 'Price|Christopher J|CJ|', 'Bower|Oliver J|OJ|', 'Stavish|Dylan|D|', 'Gokhale|Paul J|PJ|', 'Hewitt|Zoe|Z|', 'El-Khamisy|Sherif F|SF|', 'Barbaric|Ivana|I|', 'Andrews|Peter W|PW|']
D002460:Cell Line D003470:Culture Media D019610:Cytoprotection D004249:DNA Damage D004261:DNA Replication D042822:Genomic Instability D006801:Humans D008938:Mitosis D009705:Nucleosides D039904:Pluripotent Stem Cells
nucleosides human pluripotent DNA damage replication stress errors mitotic