ALBERT

Description: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Dalit Ben-Yosef , Francesca S. Boscolo , Hadar Amir , Mira Malcov , Ami Amit , Louise C. Laurent Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs. Graphical abstract Teaser Human embryonic stem cells (hESCs) are potential sources of cells for transplantation therapy. However, given the association between mutations and cancer, the frequency of genetic aberrations observed in hESCs is concerning. Using unique pedigrees of hESC lines, Laurent and colleagues now find that aberrations that occur during cell-line derivation are mainly deletions and loss of heterozygosity, whereas duplications arise more commonly during long-term culture. These results highlight the need for improved methods for derivation and culture that preserve the genetic integrity of hESCs.