Quality control Genome maintenance in pluripotent stem cells

Correspondence to Nissim Benvenisty: nissimb@cc.huji.ac.il; or Uri Ben-David: uri.ben-david@mail.huji.ac.il Abbreviations used in this paper: CNV, copy number variation; DSB, doublestrand break; ESC, embryonic stem cell; hPSC, human PSC; iPSC, induced PSC; IR, ionizing radiation; mESC, mouse ESC; NHEJ, nonhomologous end joining; PSC, pluripotent stem cell; ROS, reactive oxygen species; SNV, single nucleotide variation. Pluripotent stem cells (PSCs) can be obtained from the inner cell mass of the embryonic blastocyst, resulting in embryonic stem cells (ESCs), or by reprogramming somatic cells into a pluripotent state (iPSCs). Pluripotent cells can self-renew indefinitely without losing their cellular identity, and can also differentiate into all the different cell types of the embryo. Importantly, while the latter trait is an inherent characteristic of pluripotent cells by definition, the former is actually a culture artifact, as pluripotent cells exist only transiently in vivo. Maintaining a proper genomic content is crucial for proper embryonic development in vivo, and is also critical for most applications of PSCs, such as cell therapy, disease modeling, and research of early development. Hence, it is important to understand the genome maintenance challenges that PSCs cope with, to characterize the recurrent genomic aberrations that they acquire, and to identify their functional consequences, in order to monitor, and potentially minimize, these genomic abnormalities.