title: Genetic instability in human embryonic stem cells: prospects and caveats.
abstract: Human embryonic stem cells (hESCs) display a leaky G1/S checkpoint and inefficient nucleotide excision repair activity. Maintenance of genomic stability in these cells mostly relies on the elimination of damaged cells by high rates of apoptosis. However, a subpopulation survives and proliferates actively, bypassing DNA damage by translesion synthesis, a known mutagenic process. Indeed, high levels of damage-induced mutations were observed in hESCs, similar to those in repair-deficient cells. The surviving cells also become more resistant to further damage, leading to a progressive enrichment of cultures in mutant cells. In long-term cultures, hESCs display features characteristic of neoplastic progression, including chromosomal anomalies often similar to those observed in embryo carcinoma. The implication of these facts for stem cell-based therapy and cancer research are discussed.
authors.affiliation: Institute for Cancer Studies, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. t.nouspikel@sheffield.ac.uk
authors.forename: Thierry
authors.initials: T
authors.lastname: Nouspikel
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002869:Chromosome Aberrations; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D009154:Mutation