Derivation and differentiation of haploid human embryonic stem cells

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 species1-6, but haploid human...
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Autor*in:	Ido Sagi [verfasserIn] Gloryn Chia Tamar Golan-Lev Mordecai Peretz Uri Weissbein Lina Sui Mark V Sauer Ofra Yanuka Dieter Egli Nissim Benvenisty

Format:	Artikel
Sprache:	Englisch

Erschienen:	2016

Schlagwörter:	Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics

Übergeordnetes Werk:	Enthalten in: Nature - London : Macmillan Publishers Limited, part of Springer Nature, 1869, 532(2016), 7597, Seite 107
Übergeordnetes Werk:	volume:532 ; year:2016 ; number:7597 ; pages:107

Links:	Volltext Link aufrufen Link aufrufen

DOI / URN:	10.1038/nature17408

Katalog-ID:	OLC1975199731

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allfields	10.1038/nature17408 doi PQ20160610 (DE-627)OLC1975199731 (DE-599)GBVOLC1975199731 (PRQ)g1343-e48d3cbbbdbb35dc6e38d0a26335efe5287de1b61a91c7e7efbcff6e40f4db750 (KEY)0072945020160000532759700107derivationanddifferentiationofhaploidhumanembryoni DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Ido Sagi verfasserin aut Derivation and differentiation of haploid human embryonic stem cells 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier 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 species1-6, 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. Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics Gloryn Chia oth Tamar Golan-Lev oth Mordecai Peretz oth Uri Weissbein oth Lina Sui oth Mark V Sauer oth Ofra Yanuka oth Dieter Egli oth Nissim Benvenisty oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 532(2016), 7597, Seite 107 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:532 year:2016 number:7597 pages:107 http://dx.doi.org/10.1038/nature17408 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26982723 http://search.proquest.com/docview/1780817918 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 532 2016 7597 107
spelling	10.1038/nature17408 doi PQ20160610 (DE-627)OLC1975199731 (DE-599)GBVOLC1975199731 (PRQ)g1343-e48d3cbbbdbb35dc6e38d0a26335efe5287de1b61a91c7e7efbcff6e40f4db750 (KEY)0072945020160000532759700107derivationanddifferentiationofhaploidhumanembryoni DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Ido Sagi verfasserin aut Derivation and differentiation of haploid human embryonic stem cells 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier 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 species1-6, 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. Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics Gloryn Chia oth Tamar Golan-Lev oth Mordecai Peretz oth Uri Weissbein oth Lina Sui oth Mark V Sauer oth Ofra Yanuka oth Dieter Egli oth Nissim Benvenisty oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 532(2016), 7597, Seite 107 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:532 year:2016 number:7597 pages:107 http://dx.doi.org/10.1038/nature17408 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26982723 http://search.proquest.com/docview/1780817918 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 532 2016 7597 107
allfields_unstemmed	10.1038/nature17408 doi PQ20160610 (DE-627)OLC1975199731 (DE-599)GBVOLC1975199731 (PRQ)g1343-e48d3cbbbdbb35dc6e38d0a26335efe5287de1b61a91c7e7efbcff6e40f4db750 (KEY)0072945020160000532759700107derivationanddifferentiationofhaploidhumanembryoni DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Ido Sagi verfasserin aut Derivation and differentiation of haploid human embryonic stem cells 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier 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 species1-6, 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. Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics Gloryn Chia oth Tamar Golan-Lev oth Mordecai Peretz oth Uri Weissbein oth Lina Sui oth Mark V Sauer oth Ofra Yanuka oth Dieter Egli oth Nissim Benvenisty oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 532(2016), 7597, Seite 107 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:532 year:2016 number:7597 pages:107 http://dx.doi.org/10.1038/nature17408 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26982723 http://search.proquest.com/docview/1780817918 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 532 2016 7597 107
allfieldsGer	10.1038/nature17408 doi PQ20160610 (DE-627)OLC1975199731 (DE-599)GBVOLC1975199731 (PRQ)g1343-e48d3cbbbdbb35dc6e38d0a26335efe5287de1b61a91c7e7efbcff6e40f4db750 (KEY)0072945020160000532759700107derivationanddifferentiationofhaploidhumanembryoni DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Ido Sagi verfasserin aut Derivation and differentiation of haploid human embryonic stem cells 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier 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 species1-6, 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. Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics Gloryn Chia oth Tamar Golan-Lev oth Mordecai Peretz oth Uri Weissbein oth Lina Sui oth Mark V Sauer oth Ofra Yanuka oth Dieter Egli oth Nissim Benvenisty oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 532(2016), 7597, Seite 107 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:532 year:2016 number:7597 pages:107 http://dx.doi.org/10.1038/nature17408 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26982723 http://search.proquest.com/docview/1780817918 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 532 2016 7597 107
allfieldsSound	10.1038/nature17408 doi PQ20160610 (DE-627)OLC1975199731 (DE-599)GBVOLC1975199731 (PRQ)g1343-e48d3cbbbdbb35dc6e38d0a26335efe5287de1b61a91c7e7efbcff6e40f4db750 (KEY)0072945020160000532759700107derivationanddifferentiationofhaploidhumanembryoni DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Ido Sagi verfasserin aut Derivation and differentiation of haploid human embryonic stem cells 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier 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 species1-6, 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. Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics Gloryn Chia oth Tamar Golan-Lev oth Mordecai Peretz oth Uri Weissbein oth Lina Sui oth Mark V Sauer oth Ofra Yanuka oth Dieter Egli oth Nissim Benvenisty oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 532(2016), 7597, Seite 107 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:532 year:2016 number:7597 pages:107 http://dx.doi.org/10.1038/nature17408 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26982723 http://search.proquest.com/docview/1780817918 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 532 2016 7597 107
language	English
source	Enthalten in Nature 532(2016), 7597, Seite 107 volume:532 year:2016 number:7597 pages:107
sourceStr	Enthalten in Nature 532(2016), 7597, Seite 107 volume:532 year:2016 number:7597 pages:107
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics
dewey-raw	070
isfreeaccess_bool	false
container_title	Nature
authorswithroles_txt_mv	Ido Sagi @@aut@@ Gloryn Chia @@oth@@ Tamar Golan-Lev @@oth@@ Mordecai Peretz @@oth@@ Uri Weissbein @@oth@@ Lina Sui @@oth@@ Mark V Sauer @@oth@@ Ofra Yanuka @@oth@@ Dieter Egli @@oth@@ Nissim Benvenisty @@oth@@
publishDateDaySort_date	2016-01-01T00:00:00Z
hierarchy_top_id	129292834
dewey-sort	270
id	OLC1975199731
language_de	englisch
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author	Ido Sagi
spellingShingle	Ido Sagi ddc 070 ddc 500 fid BIODIV misc Flow cytometry misc Genomes misc Gene expression misc Chromosomes misc Stem cells misc Mammals misc Genetic engineering misc Cell cycle misc Deoxyribonucleic acid--DNA misc Epigenetics misc Genetic Association Studies - methods misc Germ Layers - cytology misc Pluripotent Stem Cells - cytology misc X Chromosome Inactivation - genetics misc Chromosomes, Human, X - genetics misc Human Embryonic Stem Cells - metabolism misc Down-Regulation - genetics misc Human Embryonic Stem Cells - cytology misc Pluripotent Stem Cells - metabolism misc Oocytes - metabolism misc Embryonic stem cells misc Genomics Derivation and differentiation of haploid human embryonic stem cells
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topic_title	070 500 DNB 500 AVZ BIODIV fid Derivation and differentiation of haploid human embryonic stem cells Flow cytometry Genomes Gene expression Chromosomes Stem cells Mammals Genetic engineering Cell cycle Deoxyribonucleic acid--DNA Epigenetics Genetic Association Studies - methods Germ Layers - cytology Pluripotent Stem Cells - cytology X Chromosome Inactivation - genetics Chromosomes, Human, X - genetics Human Embryonic Stem Cells - metabolism Down-Regulation - genetics Human Embryonic Stem Cells - cytology Pluripotent Stem Cells - metabolism Oocytes - metabolism Embryonic stem cells Genomics
topic	ddc 070 ddc 500 fid BIODIV misc Flow cytometry misc Genomes misc Gene expression misc Chromosomes misc Stem cells misc Mammals misc Genetic engineering misc Cell cycle misc Deoxyribonucleic acid--DNA misc Epigenetics misc Genetic Association Studies - methods misc Germ Layers - cytology misc Pluripotent Stem Cells - cytology misc X Chromosome Inactivation - genetics misc Chromosomes, Human, X - genetics misc Human Embryonic Stem Cells - metabolism misc Down-Regulation - genetics misc Human Embryonic Stem Cells - cytology misc Pluripotent Stem Cells - metabolism misc Oocytes - metabolism misc Embryonic stem cells misc Genomics
topic_unstemmed	ddc 070 ddc 500 fid BIODIV misc Flow cytometry misc Genomes misc Gene expression misc Chromosomes misc Stem cells misc Mammals misc Genetic engineering misc Cell cycle misc Deoxyribonucleic acid--DNA misc Epigenetics misc Genetic Association Studies - methods misc Germ Layers - cytology misc Pluripotent Stem Cells - cytology misc X Chromosome Inactivation - genetics misc Chromosomes, Human, X - genetics misc Human Embryonic Stem Cells - metabolism misc Down-Regulation - genetics misc Human Embryonic Stem Cells - cytology misc Pluripotent Stem Cells - metabolism misc Oocytes - metabolism misc Embryonic stem cells misc Genomics
topic_browse	ddc 070 ddc 500 fid BIODIV misc Flow cytometry misc Genomes misc Gene expression misc Chromosomes misc Stem cells misc Mammals misc Genetic engineering misc Cell cycle misc Deoxyribonucleic acid--DNA misc Epigenetics misc Genetic Association Studies - methods misc Germ Layers - cytology misc Pluripotent Stem Cells - cytology misc X Chromosome Inactivation - genetics misc Chromosomes, Human, X - genetics misc Human Embryonic Stem Cells - metabolism misc Down-Regulation - genetics misc Human Embryonic Stem Cells - cytology misc Pluripotent Stem Cells - metabolism misc Oocytes - metabolism misc Embryonic stem cells misc Genomics
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title	Derivation and differentiation of haploid human embryonic stem cells
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title_full	Derivation and differentiation of haploid human embryonic stem cells
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title_sort	derivation and differentiation of haploid human embryonic stem cells
title_auth	Derivation and differentiation of haploid human embryonic stem cells
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 species1-6, 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.
abstractGer	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 species1-6, 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.
abstract_unstemmed	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 species1-6, 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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title_short	Derivation and differentiation of haploid human embryonic stem cells
url	http://dx.doi.org/10.1038/nature17408 http://www.ncbi.nlm.nih.gov/pubmed/26982723 http://search.proquest.com/docview/1780817918
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author2	Gloryn Chia Tamar Golan-Lev Mordecai Peretz Uri Weissbein Lina Sui Mark V Sauer Ofra Yanuka Dieter Egli Nissim Benvenisty
author2Str	Gloryn Chia Tamar Golan-Lev Mordecai Peretz Uri Weissbein Lina Sui Mark V Sauer Ofra Yanuka Dieter Egli Nissim Benvenisty
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Derivation and differentiation of haploid human embryonic stem cells

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