Current advances in haploid stem cells

Abstract

Diploidy is the typical genomic mode in all mammals. Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells, which combine the characteristics of haploidy with a broad developmental potential and open the possibility to uncover biological mysteries at a genomic scale. To date, a multitude of haploid stem cell types from mouse, rat, monkey and humans have been derived, as more are in development. They have been applied in high-throughput genetic screens and mammalian assisted reproduction. Here, we review the generation, unique properties and broad applications of these remarkable cells.

Applications of piggyBac Transposons for Genome Manipulation in Stem Cells

“…Stem Cell Characteristic-Related Screening. Due to the infinite self-renewal ability and haploid properties, haESCs have become powerful tools for generating a tremendous number of homozygous mutation pools [117]. The PB transposon system has also been successfully applied to haESCs to identify different mechanisms of stemness and differentiation.…”

“…In addition, the combination 4 Stem Cells International of PB with newly established haploid stem cell lines from other cell types also plays a vital role in the study of lineage-specific functional genomics. Recently, Cui et al generated mouse parthenogenetic haploid trophoblast stem cells (haTSCs), which can also serve as a powerful tool for forward genetic screens in placental biology and disorders [117]. In another study, Peng et al obtained haploidinduced trophoblast stem cells (haiTSCs) from p53-deficient haESCs by overexpressing the Cdx2 gene in vitro.…”

High-throughput screening in postimplantation haploid epiblast stem cells reveals Hs3st3b1 as a modulator for reprogramming

“…Mammalian haploid cell lines have raised extensive concerns over the past decade for their advantages of generating homozygous genotypes, which are widely used for forward and reverse genetic screening 1,2 . Haploid embryonic stem cells (haESCs) are pluripotent stem cells with a single set of chromosomes, 3 serving as a convenient platform to elucidate targeting genes of important biological processes including differentiation 4 and X chromosome inactivation (XCI) 5 .…”

“…Mammalian haploid cell lines have raised extensive concerns over the past decade for their advantages of generating homozygous genotypes, which are widely used for forward and reverse genetic screening. 1,2 Haploid embryonic stem cells (haESCs) are pluripotent stem cells with a single set of chromosomes, 3 serving as a convenient platform to elucidate targeting genes of important biological processes including differentiation 4 and X chromosome inactivation (XCI). 5 Besides, haESCs also have advantages in finding out targeting genes of highly poisonous toxicant 6,7 because of their homozygous phenotype feature, thus are useful for studying molecular mechanisms behind these potential bioweapons.…”

A Genetic Screen Identifies Etl4-Deficiency Capable of Stabilizing the Haploidy in Embryonic Stem Cells

“…Recently, haploid embryonic stem cells (haESCs) have been generated in various organisms ranging from mouse to human ( Elling et al., 2011 ; Leeb and Wutz, 2011 ; Li et al., 2012 ; Sagi et al., 2016 ; Yang et al., 2012 ). As they possess only one set of chromosomes, it is quite convenient to generate loss-of-function mutations in haploid cells, and this method holds great promise for forward genetic screening ( Cui et al., 2020 ; Yilmaz et al., 2016 ).…”