Haploid embryonic stem cells: an ideal tool for mammalian genetic analyses

Abstract

Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology. However, the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic approaches. Recently, mouse haploid embryonic stem (haES) cells have been successfully isolated from parthenogenetic and androgenetic embryos, providing an ideal tool for genetic analyses. In these studies, mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous recombination. In particular, haES cells from androgenetic embryos can be employed as novel, renewable form of fertilization agent for yielding live-born mice via injection into oocytes, thus showing the possibility that genetic analysis can be extended from cellular level to organism level.

Generation of haploid embryonic stem cells from Macaca fascicularis monkey parthenotes

“…However, the aneuploidy and cancerous characters of these cells have limited applications 6 in both basic and applied research. Here, we established two haploid ESC lines from monkey PG blastocysts, indicating the feasibility of generation of normal haploid cell lines from primates.…”

“…For example, the budding yeast Saccharomyces cerevisiae has been largely utilized as a model organism to understand important biological processes 1 . Recently, mouse haploid embryonic stem cells (haESCs) have been successfully derived from parthenogenetic (PG) 2,3 and androgenetic (AG) 4,5 blastocysts, and applied to forward or reverse genetic screening 2,3 and production of genetically modified mice 4,5 , showing a great potential in genetic studies in mammalian organisms 6 . The success in mouse raises a particular challenging question of whether haESCs can be established in non-human primates.…”

SIRT1 regulates autophagy and diploidization in parthenogenetic haploid embryonic stem cells

“…As previously reported, we generated 147 parthenogenetic haploid morulaes from the mature MII oocytes after treatment with 5 mM Srcl 2 [2,4,5]. Finally, 13 ph ESCs line (named respectively HAP-1…13) was obtained and subsequently expanded for over 35 passages.…”

“…Since 2011, several research groups have independently established haploid embryonic stem cells (hESCs) successfully from mouse haploid parthenogenetic or androgenetic embryos [2,3]. Abundant data show that hESCs can offer new possibilities for genetic screening analyses, further produce genetic models for recessive traits, development and disease studies in vitro or in vivo [4,5].…”

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].…”