In somatic cells of female mammals, one of the two X chromosomes is inactivated and forms facultative heterochromatin that is stably maintained throughout somatic cell divisions. At the time of onset of meiosis, however, reversal of X chromosome inactivation occurs in female primordial germ cells. This phenomenon, X chromosome reactivation, can be recapitulated by distinct experimental procedures: (1) embryonic stem (ES) or embryonal carcinoma (EC) cell-fusion with female somatic cells, (2) induced pluripotent stem (iPS) cells derived from somatic cells by ectopic expression of several transcription factors, and (3) spontaneous X chromosome reactivation in a rare EC cell line that retained the inactive X chromosome. Using a combination of cell and molecular biology, we are studying the molecular basis of X chromosome reactivation in vivo and in vitro. We are particularly interested in the relationship between spontaneous X-reactivation and stochastic appearance of stem-like precursor cells in the EC cell culture.