| 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
|
| Resource |
| DNA material |
pBlKS hCMV*-1 b-globinpA (RDB09232). |
