Although cell-fate decisions are fairly stable in vivo, somatic cells can be reprogrammed back into pluripotency in vitro by ectopic expression of defined transcription factors (Takahashi and Yamanaka, 2006). Successful reprogramming requires complete erasure of somatic cell memory and establishment of a pluripotent stem cell epigenetic landscape (Nashun et al., 2015). Fibroblasts and peripheral blood mononuclear cells (PBMCs) are commonly used for reprogramming (Santostefano et al., 2015). Induced pluripotent stem cells (iPSCs) are known to be epigenetically similar to human embryonic stem cells (hESCs) (Guenther et al., 2010, Maherali et al., 2007), although several reports have suggested retention of epigenetic memory related to the cell of origin (Bar-Nur et al., 2011, Kim et al., 2010, Kim et al., 2011, Ohi et al., 2011, Polo et al., 2010). This phenomenon can have functional consequences by influencing iPSC differentiation propensity and biasing it toward the cell type of origin at the expense of other lineages (Bar-Nur et al., 2011, Kim et al., 2010, Polo et al., 2010). However, conflicting studies have shown that variations in directed differentiation (Kajiwara et al., 2012) and transcriptional heterogeneity (Rouhani et al., 2014) between iPSC lines were ascribed to the genetic background of the donor.
