@article{TEXTUAL,
      recid = {10862},
      author = {Garitaonandia, Ibon and Amir, Hadar and Sesillo Boscolo,  Francesca and Wambua, Gerald K. and Schultheisz, Heather L.  and Sabatini, Karen and Morey, Robert and Waltz, Shannon  and Wang, Yu-Chieh and Tran, Ha and Leonardo, Trevor R. and  Nazor, Kristopher and Slavin, Ileana and Lynch, Candace and  Li, Yingchun and Coleman, Ronald and Gallego Romero, Irene  and Altun, Gulsah and Reynolds, David and Parast, Mana},
      title = {Increased Risk of Genetic and Epigenetic Instability in  Human Embryonic Stem Cells Associated with Specific Culture  Conditions},
      journal = {PLOS ONE},
      address = {2015-02-25},
      number = {TEXTUAL},
      abstract = {The self-renewal and differentiation capacities of human  pluripotent stem cells (hPSCs) make them a promising source  of material for cell transplantation therapy, drug  development, and studies of cellular differentiation and  development. However, the large numbers of cells necessary  for many of these applications require extensive expansion  of hPSC cultures, a process that has been associated with  genetic and epigenetic alterations. We have performed a  combinatorial study on both hESCs and hiPSCs to compare the  effects of enzymatic vs. mechanical passaging, and  feeder-free vs. mouse embryonic fibroblast feeder  substrate, on the genetic and epigenetic stability and the  phenotypic characteristics of hPSCs. In extensive  experiments involving over 100 continuous passages, we  observed that both enzymatic passaging and feeder-free  culture were associated with genetic instability, higher  rates of cell proliferation, and persistence of  OCT4/POU5F1-positive cells in teratomas, with enzymatic  passaging having the stronger effect. In all combinations  of culture conditions except for mechanical passaging on  feeder layers, we noted recurrent deletions in the genomic  region containing the tumor suppressor gene TP53, which was  associated with decreased mRNA expression of TP53, as well  as alterations in the expression of several downstream  genes consistent with a decrease in the activity of the  TP53 pathway. Among the hESC cultures, we also observed  culture-associated variations in global gene expression and  DNA methylation. The effects of enzymatic passaging and  feeder-free conditions were also observed in hiPSC  cultures. Our results highlight the need for careful  assessment of the effects of culture conditions on cells  intended for clinical therapies.},
      url = {http://knowledge.uchicago.edu/record/10862},
}