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Biotech / Medical : STEM -- StemCells, Inc.
STEM 15.24-1.0%11:11 AM EST
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To: tom pope who wrote (515)8/23/2000 11:50:47 AM
From: scaram(o)uche  Read Replies (1) of 805
 
Tom:

Here' the BTRN-related work (patent to SCS, PTY.). My daughter gets back from a summer in Japan today, and I'm outta here. Won't be able to do further pointing today......

Nat Genet 2000 Apr;24(4):372-6
Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.

Niwa H, Miyazaki J, Smith AG

Centre for Genome Research, The University of Edinburgh, King's Buildings, Edinburgh, UK.

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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