Haploid mouse germ cell precursors from embryonic stem cells revealXistactivation from a single X chromosome

Abstract

In mammals, one of the two X chromosomes of diploid female cells is inactivated for gene dosage compensation between the sexes. Xist initiates X chromosome inactivation (XCI) in female cells. Although Xist is not expressed in male cells with a single X chromosome, it remains unclear if a single X chromosome in a haploid cell would lead to Xist activation. Haploid embryonic stem cells (haESCs) have been derived from several mammalian species, and maintain pluripotency in culture. They also show a predisposition for diploidization especially during differentiation. Establishing somatic haploid cells has been reported by inhibiting potential factors for diploidization. Considering high diploidization in somatic lineages, we wondered if specification of germline progenitor cells could be less restrictive to a haploid genome. Here, we report that mouse primordial germ cell-like cells (PGCLCs) preferentially maintain a haploid genome. Using this differentiation system, we find that Xist is initially induced in differentiating haESCs but subsides later after germ cell specification. The observation that XCI is initiated in haploid cells demonstrates Xist activation without the requirement of a second X chromosome inactivation center (Xic).