Figure 5. Effects of X chromosome instability on disease modeling.

Reprogramming of differentiated cells from females heterozygous for an X-linked mutation results in iPSC lines that either express the mutant or the wildtype allele from the Xa at early passage due to non-random X-inactivation. These cell lines represent pairs of experimental and control cells ideal for modeling X-linked disease on an isogenic background. However, upon XIST loss and Xi erosion, the allele from the Xi can become re-expressed, resulting in the loss or modulation of the disease phenotype.