X chromosome reactivation in female mouse germ cells is essential for the transmission of one active X chromosome to the progeny. However, despite its key role in development, the mechanistic details and kinetics still remain elusive, as previous studies were restricted by a scarcity of cells in vivo and a lack of adequate in vitro systems. Here, I present the characterization of X-chromosome dynamics during germ cell formation through the use of a tailor-made in vitro system, which facilitates accurate profiling of X-chromosome activity. We recapitulate X-inactivation starting in epiblast-like cells (EpiLCs) and follow its dynamics in the progression to primordial germ cell-like cells (PGCLCs), followed by X-reactivation in germ cells upon meiotic entry. We show that PGCLCs undergoing X-inactivation can enter meiosis more efficiently, whilst PGCLCs bypassing X-inactivation and therefore also lacking subsequent X-reactivation, show a reduced meiotic potential. We conclude that tracing the X chromosome status during germ cell formation facilitates the dissection of the relationship between X chromosome dynamics and proper germline fate acquisition.
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