論文 - 詳細
| RRC ID | 50600 |
|---|---|
| 著者 | Niwa H, Miyazaki J, Smith AG. |
| タイトル | Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. |
| ジャーナル | Nat Genet |
| Abstract |
Cell fate during development is defined by transcription factors that act as molecular switches to activate or repress specific gene expression programmes. The POU transcription factor Oct-3/4 (encoded by Pou5f1) is a candidate regulator in pluripotent and germline cells and is essential for the initial formation of a pluripotent founder cell population in the mammalian embryo. Here we use conditional expression and repression in embryonic stem (ES) cells to determine requirements for Oct-3/4 in the maintenance of developmental potency. Although transcriptional determination has usually been considered as a binary on-off control system, we found that the precise level of Oct-3/4 governs three distinct fates of ES cells. A less than twofold increase in expression causes differentiation into primitive endoderm and mesoderm. In contrast, repression of Oct-3/4 induces loss of pluripotency and dedifferentiation to trophectoderm. Thus a critical amount of Oct-3/4 is required to sustain stem-cell self-renewal, and up- or downregulation induce divergent developmental programmes. Our findings establish a role for Oct-3/4 as a master regulator of pluripotency that controls lineage commitment and illustrate the sophistication of critical transcriptional regulators and the consequent importance of quantitative analyses. |
| 巻・号 | 24(4) |
| ページ | 372-6 |
| 公開日 | 2000-4-1 |
| DOI | 10.1038/74199 |
| PMID | 10742100 |
| MeSH | Animals Cell Differentiation Cell Division Cell Line Cell Lineage Clone Cells / cytology Clone Cells / metabolism DNA-Binding Proteins / biosynthesis* DNA-Binding Proteins / genetics Down-Regulation / genetics Gene Expression Regulation, Developmental* Genes, Regulator* Genes, Reporter Mice Octamer Transcription Factor-3 RNA, Messenger / biosynthesis Stem Cells / cytology* Stem Cells / metabolism Transcription Factors / biosynthesis* Transcription Factors / genetics Transcription Factors / metabolism Transcription, Genetic / genetics Transfection Up-Regulation / genetics |
| IF | 27.605 |
| 引用数 | 2537 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 136 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 遺伝子材料 | pBlKS hCMV*-1 b-globinpA (RDB09232). |