Reference - Detail
| RRC ID | 50600 |
|---|---|
| Author | Niwa H, Miyazaki J, Smith AG. |
| Title | Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. |
| Journal | 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. |
| Volume | 24(4) |
| Pages | 372-6 |
| Published | 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 |
| Times Cited | 2537 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 136 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| DNA material | pBlKS hCMV*-1 b-globinpA (RDB09232). |