Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling
文献类型：期刊论文
| 作者 | Zhu, WQ; Yao, X; Liang, Y; Liang, D; Song, L; Jing, NH; Li, JS; Wang, G |
| 刊名 | DEVELOPMENT
 |
| 出版日期 | 2015 |
| 卷号 | 142期号:3页码:465-476 |
| 关键词 | BMP signaling ETS1 MED23 Mediator Embryonic stem cells Neural differentiation |
| 通讯作者 | Wang, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,gwang@sibcb.ac.cn |
| 英文摘要 | Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. |
| 学科主题 | Developmental Biology |
| 类目[WOS] | Developmental Biology |
| 关键词[WOS] | TRANSCRIPTION CONTROL ; COMPLEX ; WNT ; SUBUNIT ; FGF ; SPECIFICATION ; ZEBRAFISH ; INDUCTION ; GENE ; ADIPOGENESIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000348251800008 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/41]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhu, WQ,Yao, X,Liang, Y,et al. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling[J]. DEVELOPMENT,2015,142(3):465-476. |
| APA | Zhu, WQ.,Yao, X.,Liang, Y.,Liang, D.,Song, L.,...&Wang, G.(2015).Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.DEVELOPMENT,142(3),465-476. |
| MLA | Zhu, WQ,et al."Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling".DEVELOPMENT 142.3(2015):465-476. |
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