Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile
Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, w...
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| Autor*in: |
Sugawa, Fumihiro [verfasserIn] Araúzo‐Bravo, Marcos J [verfasserIn] Yoon, Juyong [verfasserIn] Kim, Kee‐Pyo [verfasserIn] Aramaki, Shinya [verfasserIn] Wu, Guangming [verfasserIn] Stehling, Martin [verfasserIn] Psathaki, Olympia E [verfasserIn] Hübner, Karin [verfasserIn] Schöler, Hans R [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015 |
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| Anmerkung: |
© The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 |
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| Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 34(2015), 8 vom: 06. März, Seite 1009-1024 |
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| Übergeordnetes Werk: |
volume:34 ; year:2015 ; number:8 ; day:06 ; month:03 ; pages:1009-1024 |
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| DOI / URN: |
10.15252/embj.201488049 |
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| Katalog-ID: |
SPR058012923 |
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| 245 | 1 | 0 | |a Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile |
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| 520 | |a Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. | ||
| 520 | |a Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). | ||
| 520 | |a Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. | ||
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| 700 | 1 | |a Araúzo‐Bravo, Marcos J |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Juyong |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kee‐Pyo |e verfasserin |4 aut | |
| 700 | 1 | |a Aramaki, Shinya |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Guangming |e verfasserin |4 aut | |
| 700 | 1 | |a Stehling, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Psathaki, Olympia E |e verfasserin |4 aut | |
| 700 | 1 | |a Hübner, Karin |e verfasserin |4 aut | |
| 700 | 1 | |a Schöler, Hans R |e verfasserin |4 aut | |
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10.15252/embj.201488049 doi (DE-627)SPR058012923 (SPR)embj.201488049-e DE-627 ger DE-627 rakwb eng Sugawa, Fumihiro verfasserin aut Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. BLIMP1 (dpeaa)DE-He213 human pluripotent stem cells (dpeaa)DE-He213 primordial germ cell precursors (dpeaa)DE-He213 primordial germ cell specification (dpeaa)DE-He213 Araúzo‐Bravo, Marcos J verfasserin aut Yoon, Juyong verfasserin aut Kim, Kee‐Pyo verfasserin aut Aramaki, Shinya verfasserin aut Wu, Guangming verfasserin aut Stehling, Martin verfasserin aut Psathaki, Olympia E verfasserin aut Hübner, Karin verfasserin aut Schöler, Hans R verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 34(2015), 8 vom: 06. März, Seite 1009-1024 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:34 year:2015 number:8 day:06 month:03 pages:1009-1024 https://dx.doi.org/10.15252/embj.201488049 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 34 2015 8 06 03 1009-1024 |
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10.15252/embj.201488049 doi (DE-627)SPR058012923 (SPR)embj.201488049-e DE-627 ger DE-627 rakwb eng Sugawa, Fumihiro verfasserin aut Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. BLIMP1 (dpeaa)DE-He213 human pluripotent stem cells (dpeaa)DE-He213 primordial germ cell precursors (dpeaa)DE-He213 primordial germ cell specification (dpeaa)DE-He213 Araúzo‐Bravo, Marcos J verfasserin aut Yoon, Juyong verfasserin aut Kim, Kee‐Pyo verfasserin aut Aramaki, Shinya verfasserin aut Wu, Guangming verfasserin aut Stehling, Martin verfasserin aut Psathaki, Olympia E verfasserin aut Hübner, Karin verfasserin aut Schöler, Hans R verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 34(2015), 8 vom: 06. März, Seite 1009-1024 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:34 year:2015 number:8 day:06 month:03 pages:1009-1024 https://dx.doi.org/10.15252/embj.201488049 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 34 2015 8 06 03 1009-1024 |
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10.15252/embj.201488049 doi (DE-627)SPR058012923 (SPR)embj.201488049-e DE-627 ger DE-627 rakwb eng Sugawa, Fumihiro verfasserin aut Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. BLIMP1 (dpeaa)DE-He213 human pluripotent stem cells (dpeaa)DE-He213 primordial germ cell precursors (dpeaa)DE-He213 primordial germ cell specification (dpeaa)DE-He213 Araúzo‐Bravo, Marcos J verfasserin aut Yoon, Juyong verfasserin aut Kim, Kee‐Pyo verfasserin aut Aramaki, Shinya verfasserin aut Wu, Guangming verfasserin aut Stehling, Martin verfasserin aut Psathaki, Olympia E verfasserin aut Hübner, Karin verfasserin aut Schöler, Hans R verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 34(2015), 8 vom: 06. März, Seite 1009-1024 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:34 year:2015 number:8 day:06 month:03 pages:1009-1024 https://dx.doi.org/10.15252/embj.201488049 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 34 2015 8 06 03 1009-1024 |
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10.15252/embj.201488049 doi (DE-627)SPR058012923 (SPR)embj.201488049-e DE-627 ger DE-627 rakwb eng Sugawa, Fumihiro verfasserin aut Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. BLIMP1 (dpeaa)DE-He213 human pluripotent stem cells (dpeaa)DE-He213 primordial germ cell precursors (dpeaa)DE-He213 primordial germ cell specification (dpeaa)DE-He213 Araúzo‐Bravo, Marcos J verfasserin aut Yoon, Juyong verfasserin aut Kim, Kee‐Pyo verfasserin aut Aramaki, Shinya verfasserin aut Wu, Guangming verfasserin aut Stehling, Martin verfasserin aut Psathaki, Olympia E verfasserin aut Hübner, Karin verfasserin aut Schöler, Hans R verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 34(2015), 8 vom: 06. März, Seite 1009-1024 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:34 year:2015 number:8 day:06 month:03 pages:1009-1024 https://dx.doi.org/10.15252/embj.201488049 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 34 2015 8 06 03 1009-1024 |
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10.15252/embj.201488049 doi (DE-627)SPR058012923 (SPR)embj.201488049-e DE-627 ger DE-627 rakwb eng Sugawa, Fumihiro verfasserin aut Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. BLIMP1 (dpeaa)DE-He213 human pluripotent stem cells (dpeaa)DE-He213 primordial germ cell precursors (dpeaa)DE-He213 primordial germ cell specification (dpeaa)DE-He213 Araúzo‐Bravo, Marcos J verfasserin aut Yoon, Juyong verfasserin aut Kim, Kee‐Pyo verfasserin aut Aramaki, Shinya verfasserin aut Wu, Guangming verfasserin aut Stehling, Martin verfasserin aut Psathaki, Olympia E verfasserin aut Hübner, Karin verfasserin aut Schöler, Hans R verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 34(2015), 8 vom: 06. März, Seite 1009-1024 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:34 year:2015 number:8 day:06 month:03 pages:1009-1024 https://dx.doi.org/10.15252/embj.201488049 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 34 2015 8 06 03 1009-1024 |
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Sugawa, Fumihiro @@aut@@ Araúzo‐Bravo, Marcos J @@aut@@ Yoon, Juyong @@aut@@ Kim, Kee‐Pyo @@aut@@ Aramaki, Shinya @@aut@@ Wu, Guangming @@aut@@ Stehling, Martin @@aut@@ Psathaki, Olympia E @@aut@@ Hübner, Karin @@aut@@ Schöler, Hans R @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR058012923</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20241024065123.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">241024s2015 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.15252/embj.201488049</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR058012923</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)embj.201488049-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Sugawa, Fumihiro</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks).</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. 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Sugawa, Fumihiro |
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Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile BLIMP1 (dpeaa)DE-He213 human pluripotent stem cells (dpeaa)DE-He213 primordial germ cell precursors (dpeaa)DE-He213 primordial germ cell specification (dpeaa)DE-He213 |
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Sugawa, Fumihiro Araúzo‐Bravo, Marcos J Yoon, Juyong Kim, Kee‐Pyo Aramaki, Shinya Wu, Guangming Stehling, Martin Psathaki, Olympia E Hübner, Karin Schöler, Hans R |
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Elektronische Aufsätze |
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Sugawa, Fumihiro |
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human primordial germ cell commitment in vitro associates with a unique prdm14 expression profile |
| title_auth |
Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile |
| abstract |
Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 |
| abstractGer |
Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 |
| abstract_unstemmed |
Abstract Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs.PGCLCs exhibit minimal expression of the PGC gene PRDM14.PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed.Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro. This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. © The Authors. Published under the terms of the CC BY NC ND 4.0 license 2015 |
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Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile |
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| score |
7.400687 |