Four major observations emerge from this study. First, we show that source-cell-specific differences are not retained to a significant extent in isogenic iPSC lines. This is in line with a recent report (Rouhani et al., 2014), but contrasts with earlier studies which observed disruptive retention of somatic cell memory in iPSC lines (Bar-Nur et al., 2011, Kim et al., 2010, Polo et al., 2010). Long-term culture has shown to be advantageous in erasing cell-type-specific memory (Kim et al., 2010, Polo et al., 2010), diminishing transcriptional differences between human iPSC and ESC lines (Chin et al., 2010), and eliminating genetic mosaicism (Hussein et al., 2011). In addition, we used the all-in-one type footprint free SeVdp-iPS system for generation of uniform iPSC lines (Nishimura et al., 2011). We performed molecular analyses at later passages and obtained highly similar molecular signatures for genetically matched iPSC lines derived from two different tissues, even though fibroblasts and PBMCs include multiple cell populations with distinct epigenetic and transcriptional landscapes (Sorrell and Caplan, 2004, Zhang and Huang, 2012).
