Haploid mouse germ cell precursors from embryonic stem cells reveal Xist activation from a single X chromosome

Mammalian haploid cells have applications for genetic screening and substituting gametic genomes. Here we characterize a culture system for obtaining haploid primordial germ cell-like cells (PCGLCs) from haploid mouse embryonic stem cells (ESCs). We find that a haploid genome is maintained in PGCLCs with a high frequency indicating a substantially lower rate of diploidization than somatic cells. Characterization of the differentiating haploid ESCs reveals that Xist is activated from the single X chromosome. This observation suggests that X chromosome inactivation is initiated in haploid cells consistent with a model where autosomal blocking factors set a threshold for X-linked activators. The germline segregates from the epiblast and differs from somatic lineages in gene expression and epigenetic mechanisms. The ability of primordial germ cells for repressing Xist might contribute to the maintenance of a haploid genome.