@article{TEXTUAL,
      recid = {10235},
      author = {Thomas, Samantha M. and Kagan, Courtney and Pavlovic,  Bryan J. and Burnett, Jonathan and Patterson, Kristen and  Pritchard, Jonathan K. and Gilad, Yoav},
      title = {Reprogramming LCLs to iPSCs Results in Recovery of  Donor-Specific Gene Expression Signature},
      journal = {PLOS Genetics},
      address = {2015-05-07},
      number = {TEXTUAL},
      abstract = {&lt;p&gt;Renewable &lt;em&gt;in vitro&lt;/em&gt; cell cultures, such as  lymphoblastoid cell lines (LCLs), have facilitated studies  that contributed to our understanding of genetic influence  on human traits. However, the degree to which cell lines  faithfully maintain differences in donor-specific  phenotypes is still debated. We have previously reported  that standard cell line maintenance practice results in a  loss of donor-specific gene expression signatures in LCLs.  An alternative to the LCL model is the induced pluripotent  stem cell (iPSC) system, which carries the potential to  model tissue-specific physiology through the use of  differentiation protocols. Still, existing LCL banks  represent an important source of starting material for iPSC  generation, and it is possible that the disruptions in gene  regulation associated with long-term LCL maintenance could  persist through the reprogramming process. To address this  concern, we studied the effect of reprogramming mature LCL  cultures from six unrelated donors to iPSCs on the ensuing  gene expression patterns within and between individuals. We  show that the reprogramming process results in a recovery  of donor-specific gene regulatory signatures, increasing  the number of genes with a detectable donor effect by an  order of magnitude. The proportion of variation in gene  expression statistically attributed to donor increases from  6.9% in LCLs to 24.5% in iPSCs (&lt;em&gt;P&lt;/em&gt; &lt;  10&lt;sup&gt;-15&lt;/sup&gt;). Since environmental contributions are  unlikely to be a source of individual variation in our  system of highly passaged cultured cell lines, our  observations suggest that the effect of genotype on gene  regulation is more pronounced in iPSCs than in LCLs. Our  findings indicate that iPSCs can be a powerful model system  for studies of phenotypic variation across individuals in  general, and the genetic association with variation in gene  regulation in particular. We further conclude that LCLs are  an appropriate starting material for iPSC generation.&lt;/p&gt;},
      url = {http://knowledge.uchicago.edu/record/10235},
}