Distinct SoxB1 networks are required for naïve and primed pluripotency
Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/27746 |
| _version_ | 1811181140810137600 |
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| author | Andrea Corsinotti Frederick CK Wong Tülin Tatar Iwona Szczerbinska Florian Halbritter Douglas Colby Sabine Gogolok Raphaël Pantier Kirsten Liggat Elham S Mirfazeli Elisa Hall-Ponsele Nicholas P Mullin Valerie Wilson Ian Chambers |
| author_facet | Andrea Corsinotti Frederick CK Wong Tülin Tatar Iwona Szczerbinska Florian Halbritter Douglas Colby Sabine Gogolok Raphaël Pantier Kirsten Liggat Elham S Mirfazeli Elisa Hall-Ponsele Nicholas P Mullin Valerie Wilson Ian Chambers |
| author_sort | Andrea Corsinotti |
| collection | DOAJ |
| description | Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency. |
| first_indexed | 2024-04-11T09:13:41Z |
| format | Article |
| id | doaj.art-383310e3d27d44c8aad4b1b095ff1014 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:13:41Z |
| publishDate | 2017-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-383310e3d27d44c8aad4b1b095ff10142022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2017-12-01610.7554/eLife.27746Distinct SoxB1 networks are required for naïve and primed pluripotencyAndrea Corsinotti0https://orcid.org/0000-0003-4481-0999Frederick CK Wong1Tülin Tatar2Iwona Szczerbinska3Florian Halbritter4https://orcid.org/0000-0003-2452-4784Douglas Colby5Sabine Gogolok6Raphaël Pantier7Kirsten Liggat8Elham S Mirfazeli9Elisa Hall-Ponsele10Nicholas P Mullin11Valerie Wilson12https://orcid.org/0000-0003-4182-5159Ian Chambers13https://orcid.org/0000-0003-2605-1597MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland; Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Ibaraki, JapanMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, ScotlandDeletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency.https://elifesciences.org/articles/27746PluripotencySoxtranscription factorsEmbryonic stem cellsEpiblast stem cells |
| spellingShingle | Andrea Corsinotti Frederick CK Wong Tülin Tatar Iwona Szczerbinska Florian Halbritter Douglas Colby Sabine Gogolok Raphaël Pantier Kirsten Liggat Elham S Mirfazeli Elisa Hall-Ponsele Nicholas P Mullin Valerie Wilson Ian Chambers Distinct SoxB1 networks are required for naïve and primed pluripotency eLife Pluripotency Sox transcription factors Embryonic stem cells Epiblast stem cells |
| title | Distinct SoxB1 networks are required for naïve and primed pluripotency |
| title_full | Distinct SoxB1 networks are required for naïve and primed pluripotency |
| title_fullStr | Distinct SoxB1 networks are required for naïve and primed pluripotency |
| title_full_unstemmed | Distinct SoxB1 networks are required for naïve and primed pluripotency |
| title_short | Distinct SoxB1 networks are required for naïve and primed pluripotency |
| title_sort | distinct soxb1 networks are required for naive and primed pluripotency |
| topic | Pluripotency Sox transcription factors Embryonic stem cells Epiblast stem cells |
| url | https://elifesciences.org/articles/27746 |
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