GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:10742100
| Citation |
Niwa, H, Miyazaki, J and Smith, AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat. Genet. 24:372-6 |
|---|---|
| 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. |
| Links |
PubMed Online version:10.1038/74199 |
| Keywords |
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 |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| edit table |
See also
References
See Help:References for how to manage references in GONUTS.
