Haploid Mouse Embryonic Stem Cells: Rapid Genetic Screening and Germline Transmission

Abstract

Most animal genomes are diploid, and mammalian development depends on specific adaptations that have evolved secondary to diploidy. Genomic imprinting and dosage compensation restrict haploid development to early embryos. Recently, haploid mammalian development has been reinvestigated since the establishment of haploid embryonic stem cells (ESCs) from mouse embryos. Haploid cells possess one copy of each gene, facilitating the generation of loss-of-function mutations in a single step. Recessive mutations can then be assessed in forward genetic screens. Applications of haploid mammalian cell systems in screens have been illustrated in several recent publications. Haploid ESCs are characterized by a wide developmental potential and can contribute to chimeric embryos and mice. Different strategies for introducing genetic modifications from haploid ESCs into the mouse germline have been further developed. Haploid ESCs therefore introduce new possibilities in mammalian genetics and could offer an unprecedented tool for genome exploration in the future.

Single-Cell Dynamic Analysis of Mitosis in Haploid Embryonic Stem Cells Shows the Prolonged Metaphase and Its Association with Self-diploidization

“…However, haploid embryonic stem cells (ESCs) have recently been established from both parthenogenetic and androgenetic embryos of several species (Elling et al., 2011, Leeb and Wutz, 2011, Li et al., 2012, Sagi et al., 2016, Yang et al., 2012, Yang et al., 2013). These haploid ESCs have provided exciting possibilities in many aspects (Elling et al., 2011, Li et al., 2014, Wutz, 2014, Yang et al., 2012). However, the haploid state is not stable and haploid ESCs tend to diploidize spontaneously during continuous cell passage (Elling et al., 2011, Leeb et al., 2012, Li et al., 2012, Li et al., 2014, Yang et al., 2012).…”

Haploid Human Embryonic Stem Cells: Half the Genome, Double the Value

“…Nonetheless, haploid mammalian eggs can be artificially induced to divide as early haploid embryos, which remarkably allow the derivation of self-renewing haploid embryonic stem cells (ESCs). Following the initial reports on haploid ESCs from mouse (Leeb and Wutz, 2011;Elling et al, 2011), and later from rat and monkey (reviewed in Wutz, 2014), haploid ESCs have also been recently derived from humans (Sagi et al, 2016a). Surprisingly, and as opposed to their murine counterparts that failed to differentiate into haploid somatic cells, haploid human ESCs readily differentiate into cells of all three embryonic germ layers while remaining haploid (Sagi et al, 2016a).…”

Parthenogenetic haploid embryonic stem cells efficiently support mouse generation by oocyte injection

“…Mammalian haploid embryonic stem cells (haESCs) have been recently generated from parthenogenetic and androgenetic embryos [1,2]. Both parthenogenetic haESCs (PG-haESCs) and androgenetic haESCs (AGhaESCs) can be used for cell-based reverse and forward genetic screens on a whole-genome scale [3,4].…”