ArticleNature genetics2000
Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
Article in Nature genetics, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,357 papers, 1 of them a synthesis that pooled it.
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Who cites it
1,357 citing papers in PubMed, 1 synthesis or guideline pooled it.
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1,297 more citing papers are in PubMed but not listed here.
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3 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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