Title |
Derivation and differentiation of haploid human embryonic stem cells
|
---|---|
Published in |
Nature, March 2016
|
DOI | 10.1038/nature17408 |
Pubmed ID | |
Authors |
Ido Sagi, Gloryn Chia, Tamar Golan-Lev, Mordecai Peretz, Uri Weissbein, Lina Sui, Mark V. Sauer, Ofra Yanuka, Dieter Egli, Nissim Benvenisty |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 19 | 24% |
United Kingdom | 8 | 10% |
Australia | 4 | 5% |
Canada | 3 | 4% |
Korea, Republic of | 2 | 3% |
Venezuela, Bolivarian Republic of | 2 | 3% |
Spain | 2 | 3% |
Japan | 2 | 3% |
Comoros | 1 | 1% |
Other | 8 | 10% |
Unknown | 28 | 35% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 48 | 61% |
Scientists | 24 | 30% |
Science communicators (journalists, bloggers, editors) | 4 | 5% |
Practitioners (doctors, other healthcare professionals) | 3 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | <1% |
United Kingdom | 2 | <1% |
France | 2 | <1% |
Japan | 2 | <1% |
Qatar | 1 | <1% |
Canada | 1 | <1% |
China | 1 | <1% |
Spain | 1 | <1% |
Unknown | 327 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 79 | 23% |
Student > Ph. D. Student | 69 | 20% |
Student > Master | 37 | 11% |
Student > Bachelor | 25 | 7% |
Other | 23 | 7% |
Other | 60 | 18% |
Unknown | 47 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 119 | 35% |
Agricultural and Biological Sciences | 101 | 30% |
Medicine and Dentistry | 23 | 7% |
Immunology and Microbiology | 9 | 3% |
Neuroscience | 8 | 2% |
Other | 25 | 7% |
Unknown | 55 | 16% |