If hPSC-specific aberrations in genomic imprints and XCI persist through differentiation, they may impact the utility of hPSC-derived cells for cellular transplantation and disease modeling. Therefore, we assessed the status of such aberrations in undifferentiated and differentiated hPSCs. WA09 hESCs were studied before and after a 3 day spontaneous differentiation, while WA07, iPS201B7 and iPS414C.2 were studied before and after more extensive NPC and OPC differentiations. In every case, the aberrations in imprinting and XCI that were present in the starting undifferentiated hPSC populations were maintained, and no new aberrations arose during the course of differentiation (Figure 7A–B). In our collection of eleven fibroblast-derived hiPSC clones, loss of XCI was observed in 49 X-linked disease genes by late passage (OMIM; Figure 7C). These results merit caution in the use of female hiPSCs for studies of X-linked disease modeling.
