Coordination of EZH2 and SOX2 specifies human neural fate decision
Abstract Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq,...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2021-09-01
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| Series: | Cell Regeneration |
| Online Access: | https://doi.org/10.1186/s13619-021-00092-6 |
| _version_ | 1818586725024268288 |
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| author | Yuan Zhao Tianyu Wang Yanqi Zhang Liang Shi Cong Zhang Jingyuan Zhang Jiao Yao Qianyu Chen Xiaofen Zhong Yanxing Wei Yongli Shan Guangjin Pan |
| author_facet | Yuan Zhao Tianyu Wang Yanqi Zhang Liang Shi Cong Zhang Jingyuan Zhang Jiao Yao Qianyu Chen Xiaofen Zhong Yanxing Wei Yongli Shan Guangjin Pan |
| author_sort | Yuan Zhao |
| collection | DOAJ |
| description | Abstract Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq, ChIP-seq, et al., we uncover that EZH2, an important PRC factor, specifies the normal neural fate decision through repressing the competing meso/endoderm program. EZH2−/− hESCs show an aberrant re-activation of meso/endoderm genes during neural induction. At the molecular level, EZH2 represses meso/endoderm genes while SOX2 activates the neural genes to coordinately specify the normal neural fate. Moreover, EZH2 also supports the proliferation of human neural progenitor cells (NPCs) through repressing the aberrant expression of meso/endoderm program during culture. Together, our findings uncover the coordination of epigenetic regulators such as EZH2 and lineage factors like SOX2 in normal neural fate decision. |
| first_indexed | 2024-12-16T08:57:31Z |
| format | Article |
| id | doaj.art-2e8403b28ef746ae845f20e6e16e92b1 |
| institution | Directory Open Access Journal |
| issn | 2045-9769 |
| language | English |
| last_indexed | 2024-12-16T08:57:31Z |
| publishDate | 2021-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Cell Regeneration |
| spelling | doaj.art-2e8403b28ef746ae845f20e6e16e92b12022-12-21T22:37:15ZengSpringerOpenCell Regeneration2045-97692021-09-0110111310.1186/s13619-021-00092-6Coordination of EZH2 and SOX2 specifies human neural fate decisionYuan Zhao0Tianyu Wang1Yanqi Zhang2Liang Shi3Cong Zhang4Jingyuan Zhang5Jiao Yao6Qianyu Chen7Xiaofen Zhong8Yanxing Wei9Yongli Shan10Guangjin Pan11CAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesBiomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNanfang Hospital, Southern Medical UniversityCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesAbstract Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq, ChIP-seq, et al., we uncover that EZH2, an important PRC factor, specifies the normal neural fate decision through repressing the competing meso/endoderm program. EZH2−/− hESCs show an aberrant re-activation of meso/endoderm genes during neural induction. At the molecular level, EZH2 represses meso/endoderm genes while SOX2 activates the neural genes to coordinately specify the normal neural fate. Moreover, EZH2 also supports the proliferation of human neural progenitor cells (NPCs) through repressing the aberrant expression of meso/endoderm program during culture. Together, our findings uncover the coordination of epigenetic regulators such as EZH2 and lineage factors like SOX2 in normal neural fate decision.https://doi.org/10.1186/s13619-021-00092-6 |
| spellingShingle | Yuan Zhao Tianyu Wang Yanqi Zhang Liang Shi Cong Zhang Jingyuan Zhang Jiao Yao Qianyu Chen Xiaofen Zhong Yanxing Wei Yongli Shan Guangjin Pan Coordination of EZH2 and SOX2 specifies human neural fate decision Cell Regeneration |
| title | Coordination of EZH2 and SOX2 specifies human neural fate decision |
| title_full | Coordination of EZH2 and SOX2 specifies human neural fate decision |
| title_fullStr | Coordination of EZH2 and SOX2 specifies human neural fate decision |
| title_full_unstemmed | Coordination of EZH2 and SOX2 specifies human neural fate decision |
| title_short | Coordination of EZH2 and SOX2 specifies human neural fate decision |
| title_sort | coordination of ezh2 and sox2 specifies human neural fate decision |
| url | https://doi.org/10.1186/s13619-021-00092-6 |
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