Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells
The mechanisms of transcriptional regulation underlying human primordial germ cell (PGC) differentiation are largely unknown. The transcriptional repressor Prdm1/Blimp-1 is known to play a critical role in controlling germ cell specification in mice. Here, we show that PRDM1 is expressed in developi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-02-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221367111300177X |
| _version_ | 1818852688737075200 |
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| author | I-Ying Lin Feng-Lan Chiu Chen-Hsiang Yeang Hsin-Fu Chen Ching-Yu Chuang Shii-Yi Yang Pei-Shan Hou Nardnisa Sintupisut Hong-Nerng Ho Hung-Chih Kuo Kuo-I Lin |
| author_facet | I-Ying Lin Feng-Lan Chiu Chen-Hsiang Yeang Hsin-Fu Chen Ching-Yu Chuang Shii-Yi Yang Pei-Shan Hou Nardnisa Sintupisut Hong-Nerng Ho Hung-Chih Kuo Kuo-I Lin |
| author_sort | I-Ying Lin |
| collection | DOAJ |
| description | The mechanisms of transcriptional regulation underlying human primordial germ cell (PGC) differentiation are largely unknown. The transcriptional repressor Prdm1/Blimp-1 is known to play a critical role in controlling germ cell specification in mice. Here, we show that PRDM1 is expressed in developing human gonads and contributes to the determination of germline versus neural fate in early development. We show that knockdown of PRDM1 in human embryonic stem cells (hESCs) impairs germline potential and upregulates neural genes. Conversely, ectopic expression of PRDM1 in hESCs promotes the generation of cells that exhibit phenotypic and transcriptomic features of early PGCs. Furthermore, PRDM1 suppresses transcription of SOX2. Overexpression of SOX2 in hESCs under conditions favoring germline differentiation skews cell fate from the germline to the neural lineage. Collectively, our results demonstrate that PRDM1 serves as a molecular switch to modulate the divergence of neural or germline fates through repression of SOX2 during human development. |
| first_indexed | 2024-12-19T07:24:54Z |
| format | Article |
| id | doaj.art-c91af3f494cf48ddbaaad1267426c24a |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-19T07:24:54Z |
| publishDate | 2014-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-c91af3f494cf48ddbaaad1267426c24a2022-12-21T20:30:52ZengElsevierStem Cell Reports2213-67112014-02-012218920410.1016/j.stemcr.2013.12.009Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem CellsI-Ying Lin0Feng-Lan Chiu1Chen-Hsiang Yeang2Hsin-Fu Chen3Ching-Yu Chuang4Shii-Yi Yang5Pei-Shan Hou6Nardnisa Sintupisut7Hong-Nerng Ho8Hung-Chih Kuo9Kuo-I Lin10Genomics Research Center, Academia Sinica, Taipei 115, TaiwanInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, TaiwanInstitute of Statistical Science, Academia Sinica, Taipei 115, TaiwanGraduate Institute of Clinical Genomics, College of Medicine, National Taiwan University, Taipei 106, TaiwanInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, TaiwanInstitute of Statistical Science, Academia Sinica, Taipei 115, TaiwanGraduate Institute of Clinical Genomics, College of Medicine, National Taiwan University, Taipei 106, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanThe mechanisms of transcriptional regulation underlying human primordial germ cell (PGC) differentiation are largely unknown. The transcriptional repressor Prdm1/Blimp-1 is known to play a critical role in controlling germ cell specification in mice. Here, we show that PRDM1 is expressed in developing human gonads and contributes to the determination of germline versus neural fate in early development. We show that knockdown of PRDM1 in human embryonic stem cells (hESCs) impairs germline potential and upregulates neural genes. Conversely, ectopic expression of PRDM1 in hESCs promotes the generation of cells that exhibit phenotypic and transcriptomic features of early PGCs. Furthermore, PRDM1 suppresses transcription of SOX2. Overexpression of SOX2 in hESCs under conditions favoring germline differentiation skews cell fate from the germline to the neural lineage. Collectively, our results demonstrate that PRDM1 serves as a molecular switch to modulate the divergence of neural or germline fates through repression of SOX2 during human development.http://www.sciencedirect.com/science/article/pii/S221367111300177X |
| spellingShingle | I-Ying Lin Feng-Lan Chiu Chen-Hsiang Yeang Hsin-Fu Chen Ching-Yu Chuang Shii-Yi Yang Pei-Shan Hou Nardnisa Sintupisut Hong-Nerng Ho Hung-Chih Kuo Kuo-I Lin Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells Stem Cell Reports |
| title | Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells |
| title_full | Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells |
| title_fullStr | Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells |
| title_full_unstemmed | Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells |
| title_short | Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells |
| title_sort | suppression of the sox2 neural effector gene by prdm1 promotes human germ cell fate in embryonic stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S221367111300177X |
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