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Derivation of haploid embryonic stem cells from mouse embryos

Abstract

Most animals are diploid, but haploid-only and male-haploid (such as honeybee and ant) species have been described1. The diploid genomes of complex organisms limit genetic approaches in biomedical model species such as mice. To overcome this problem, experimental induction of haploidy has been used in fish2,3. Haploid development in zebrafish has been applied for genetic screening2. Recently, haploid pluripotent cell lines from medaka fish (Oryzias latipes) have also been established3. In contrast, haploidy seems less compatible with development in mammals4,5. Although haploid cells have been observed in egg cylinder stage parthenogenetic mouse embryos6, most cells in surviving embryos become diploid. Here we describe haploid mouse embryonic stem cells and show their application in forward genetic screening.

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Figure 1: Derivation of haploid ES cells.
Figure 2: Expression analysis of haploid ES cells.
Figure 3: Developmental potential of haploid ES cells.

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Acknowledgements

We thank A. Smith and J. Nichols for critical discussion; K. Jones for advice on cell culture; S. Dietmann for bioinformatics support; and R. Walker for cell sorting. We would also like to thank B. Mansfield and C.-E. Dumeau for their help, and the BSU team at the centre for maintaining the mouse colony. This work was supported by a Wellcome Trust Senior Research Fellowship to A.W. (grant reference 087530/Z/08/A) and an EMBO Long Term Fellowship to M.L.

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Authors

Contributions

M.L. performed the experiments, analysed the data and wrote the manuscript. A.W. performed some experiments, wrote the paper and supervised the study.

Corresponding author

Correspondence to Anton Wutz.

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Competing interests

A patent application covering haploid embryonic stem cells has been filed.

Additional information

Gene expression and CGH data sets can be accessed as the GEO reference series GSE30879 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30879). This series includes the GSE30744 (Expression analysis of haploid and diploid ES cells in 2i medium) and the GSE30749 (CGH analysis of haploid ES cells) data sets.

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The file contains Supplementary Figures 1-8 with legends and Supplementary Tables 1-2. (PDF 1822 kb)

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Leeb, M., Wutz, A. Derivation of haploid embryonic stem cells from mouse embryos. Nature 479, 131–134 (2011). https://doi.org/10.1038/nature10448

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