Derivation and differentiation of haploid human embryonic stem cells.

Authors:
Ido Sagi
Ido Sagi
Silberman Institute of Life Sciences
Israel
Gloryn Chia
Gloryn Chia
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry
United Kingdom
Tamar Golan-Lev
Tamar Golan-Lev
The International Stem Cell Research Institute
United States
Mordecai Peretz
Mordecai Peretz
The Azrieli Center for Stem Cells and Genetic Research
Uri Weissbein
Uri Weissbein
Brandeis University
United States
Lina Sui
Lina Sui
Vrije Universiteit Brussel
Belgium
Mark V Sauer
Mark V Sauer
Columbia University
United States
Ofra Yanuka
Ofra Yanuka
The Hebrew University
Israel

Nature 2016 Apr 16;532(7597):107-11. Epub 2016 Mar 16.

The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to ensure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but haploid human ES cells have yet to be reported. Here we generated and analysed a collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics, such as self-renewal capacity and a pluripotency-specific molecular signature. Moreover, we demonstrated the utility of these cells as a platform for loss-of-function genetic screening. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and of genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Surprisingly, we found that a haploid human genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers both in vitro and in vivo, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics and development.

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http://dx.doi.org/10.1038/nature17408DOI Listing
April 2016
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References

(Supplied by CrossRef)
Article in Nature
Leeb M. et al.
Nature 2011
Article in Cell Stem Cell
Elling U. et al.
Cell Stem Cell 2011
Article in Cell
Yang H. et al.
Cell 2012
Article in Nature
Li W. et al.
Nature 2012
Article in Cell Stem Cell
Li W. et al.
Cell Stem Cell 2014
Article in Cell Res.
Yang H. et al.
Cell Res. 2013
Article in Annu. Rev. Cell Dev. Biol.
Wutz A. et al.
Annu. Rev. Cell Dev. Biol. 2014
Article in Cell Stem Cell
Egli D. et al.
Cell Stem Cell 2011
Article in Cloning Stem Cells
Revazova E. S. et al.
Cloning Stem Cells 2007
Article in Cell Stem Cell
Kim K. et al.
Cell Stem Cell 2007
Article in Nature
Paull D. et al.
Nature 2013

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