Having the unexpected but fortuitous case of two iPSC lines made from the same individual but with contrasting ATM genotypes, we assessed baseline gene expression patterns. The results clearly indicate that the mRNA patterns affected by the lack of ATM function primarily relate to p53 pathways. In support of this interpretation, upstream regulator analysis also identified a pattern of regulation not only of the gene encoding p53 (TP53) but also the majority of transcriptional targets downstream of this key protein. It will be invaluable to continue these analyses in future studies to identify patterns of mRNA changes following the induction of DNA damage. Most important, however, the regulated mRNA patterns comparing Q3SA with Q3SC are much more focused than a comparison between unrelated cultures having the same genotypes (Q1SA versus Q3SC). Previous studies (Nayler et al., 2012) analyzed similarly diverse A-T versus control cultures and concluded that other pathways, including mitochondrial function, might be directly affected by the loss of ATM function. Our results, although identifying a core set of genes in common with those of Nayler’s study (Nayler et al., 2012), show that only by contrasting an isogenic pair of cells can the clearest functional patterns be revealed.
