Our data show that the majority of transcriptional and epigenetic signatures present in iPSCs are donor determined. This is well in line with recent studies that have suggested the influence of genetic background on transcription (Rouhani et al., 2014, Shao et al., 2013) and differentiation of iPSC lines (Kajiwara et al., 2012, Mills et al., 2013). Also, embryonic stem cells derived from individual donors are shown to maintain line-specific signatures and have distinct differentiation potentials (Bock et al., 2011, Chen et al., 2009, Osafune et al., 2008). Our present data point out that donor-dependent signatures specifically affect gene expressions involved in early embryonic lineage specification, resulting in variability between iPSC lines.