Source:http://linkedlifedata.com/resource/pubmed/id/10742100
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2000-5-4
|
| pubmed:abstractText |
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.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Octamer Transcription Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Pou5f1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
1061-4036
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
24
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
372-6
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:10742100-Animals,
pubmed-meshheading:10742100-Cell Differentiation,
pubmed-meshheading:10742100-Cell Division,
pubmed-meshheading:10742100-Cell Line,
pubmed-meshheading:10742100-Cell Lineage,
pubmed-meshheading:10742100-Clone Cells,
pubmed-meshheading:10742100-DNA-Binding Proteins,
pubmed-meshheading:10742100-Down-Regulation,
pubmed-meshheading:10742100-Gene Expression Regulation, Developmental,
pubmed-meshheading:10742100-Genes, Regulator,
pubmed-meshheading:10742100-Genes, Reporter,
pubmed-meshheading:10742100-Mice,
pubmed-meshheading:10742100-Octamer Transcription Factor-3,
pubmed-meshheading:10742100-RNA, Messenger,
pubmed-meshheading:10742100-Stem Cells,
pubmed-meshheading:10742100-Transcription, Genetic,
pubmed-meshheading:10742100-Transcription Factors,
pubmed-meshheading:10742100-Transfection,
pubmed-meshheading:10742100-Up-Regulation
|
| pubmed:year |
2000
|
| pubmed:articleTitle |
Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
|
| pubmed:affiliation |
Centre for Genome Research, The University of Edinburgh, King's Buildings, Edinburgh, UK.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|