Haploid Mouse Embryonic Stem Cells Research Articles

Germline potential of parthenogenetic haploid mouse embryonic stem cells.

Haploid embryonic stem cells (ESCs) have recently been derived from parthenogenetic mouse embryos and offer new possibilities for genetic screens. The ability of haploid ESCs to give rise to a wide range of differentiated cell types in the embryo and in vitro has been demonstrated. However, it has remained unclear whether haploid ESCs can contribute to the germline. Here, we show that parthenogenetic haploid ESCs at high passage have robust germline competence enabling the production of transgenic mouse strains from genetically modified haploid ESCs. We also show that differentiation of haploid ESCs in the embryo correlates with the gain of a diploid karyotype and that diploidisation is the result of endoreduplication and not cell fusion. By contrast, we find that a haploid karyotype is maintained when differentiation to an extra-embryonic fate is forced by induction of Gata6.

Fatherless stem cells

Two independent research groups derive haploid mouse embryonic stem cells and propose their use for genetic screens.

Forward and Reverse Genetics through Derivation of Haploid Mouse Embryonic Stem Cells

All somatic mammalian cells carry two copies of chromosomes (diploidy), whereas organisms with a single copy of their genome, such as yeast, provide a basis for recessive genetics. Here we report the generation of haploid mouse ESC lines from parthenogenetic embryos. These cells carry 20 chromosomes, express stem cell markers, and develop into all germ layers in vitro and in vivo. We also developed a reversible mutagenesis protocol that allows saturated genetic recessive screens and results in homozygous alleles. This system allowed us to generate a knockout cell line for the microRNA processing enzyme Drosha. In a forward genetic screen, we identified Gpr107 as a molecule essential for killing by ricin, a toxin being used as a bioweapon. Our results open the possibility of combining the power of a haploid genome with pluripotency of embryonic stem cells to uncover fundamental biological processes in defined cell types at a genomic scale.

Derivation of haploid embryonic stem cells from mouse embryos

Most animals are diploid but haploid-only and male-haplo species have been described 1. Diploid genomes of complex organisms limit genetic approaches in biomedical model species such as in mice. To overcome this problem experimental induction of haploidy has been used in fish 2,3. In contrast, haploidy appears less compatible with development in mammals 4,5. Here we describe haploid mouse embryonic stem cells and show their application in forward genetic screening.