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.
Original language | English |
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Pages (from-to) | 372-6 |
Number of pages | 5 |
Journal | Nature Genetics |
Volume | 24 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2000 |
Keywords
- Animals
- Cell Differentiation
- Cell Division
- Cell Line
- Cell Lineage
- Clone Cells
- DNA-Binding Proteins
- Down-Regulation
- Gene Expression Regulation, Developmental
- Genes, Regulator
- Genes, Reporter
- Mice
- Octamer Transcription Factor-3
- RNA, Messenger
- Stem Cells
- Transcription Factors
- Transcription, Genetic
- Transfection
- Up-Regulation