Derivation of Mouse Haploid Trophoblast Stem Cells

Trophoblast stem (TS) cells are increasingly used as a model system for studying placentation and placental disorders. However, practical limitations of genetic manipulation have posed challenges for genetic analysis using TS cells. Here, we report the generation of mouse parthenogenetic haploid TS cells (haTSCs) and show that supplementation with FGF4 and inhibition of Rho-associated protein kinase (ROCK) enable the maintenance of their haploidy and developmental potential. The resulting haTSCs have 20 chromosomes, exhibit typical expression features of TS cells, possess the multipotency to differentiate into specialized trophoblast cell types, and can chimerize E13.5 and term placentas. We also demonstrate the capability of the haTSCs to undergo genetic manipulation and facilitate genome-wide screening in the trophoblast lineage. We expect that haTSCs will offer a powerful tool for studying functional genomics and placental biology. [Display omitted] •Generation of mouse parthenogenetic haploid trophoblast stem cells (haTSCs)•haTSCs have 20 chromosomes and exhibit typical expression features of TS cells•haTSCs can differentiate into specialized trophoblast cell types in vitro•haTSCs can chimerize E13.5 and term placentas Trophoblast stem (TS) cells are increasingly used as a model system for studying placentation and placental disorders. Here, Cui et al. report the generation of mouse haploid TS cells, which possess a wide extraembryonic developmental potential and can serve as a powerful tool for studying functional genomics and placental biology.