Maintenance of genomic stability is crucial in ensuring cellular homeostasis and perpetuation of life. Perpetuation of the genetic information relies upon faithful replication of the genome. Mutations, generated during DNA synthesis and/or cell division and induced by exposure to external chemical agents, are drivers of genetic and associated genomic instability believed to fuel malignant transformation. Curiously, pluripotent stem cells (PSCs) are characterized by a high degree of genomic instability of unknown origin, which resembles that observed in cancer cells. This peculiar feature of PSCs raises the questions of the reasons responsible for this apparent aberrant regulation and of how genome integrity is kept under control. Genomic instability of PSCs also raises important concerns about their use in regenerative medicine, which sets severe limitations in clinical applications. The aim of this chapter is to review current knowledge about the molecular grounds of genomic instability of PSCs of diverse origin, such as embryonic (ESCs), induced pluripotent (iPSCs), and adult (ASCs) stem cells. We will also review how these features undermine the use of PSCs in clinical applications and discuss new emerging perspectives aimed at reducing genomic instability so to improve their use in clinical applications.
Part of the book: Pluripotent Stem Cells