Female human iPSCs retain an inactive X chromosome.

X chromosome inactivation refers to the silencing of on of the two X chromosomes in females. Here we studies what happens to the inactive X chromosome during reprogramming to the induced pluripotent stem cell (iPSC) state. We found that reactivation of the inactive X chromosome does not occur in human reprogramming. This is in contrast to reprogramming of mouse cells, where the inactive X reactivates. Furthermore, we showed that female human iPSCs exhibit nonrandom X chromosome inactivation, thus all cells in the population express the same X chromosome. In contrast, differentiated female cells are mosaic for which X chromosome they express. Our finding of nonrandom X chromosome inactivation in female human iPSCs will affect studies of X-linked diseases and the use of female human iPSCs.