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
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 27.125
Resource
DNA material pBlKS hCMV*-1 b-globinpA (RDB09232).