Tired and nursing a headache, and surprised that I didn't find the relevant stuff in my files when I went to look, I'll work on an answer later. Hopefully, others will beat me to it.
I'm not clear on the breadth of patent coverage either. However, I believe that SCS holds a dominant position relevant to (1) in vitro expansion of cells derived from nuclear transfer, and (2) the stem cell-specific transcription factor Oct-4. Here's a cut and paste that gives one a taste for why factors that regulate the expression of Oct-4 might be of interest. The work by Smith et al., licensed by SCS, follows........
Stem Cells 2001;19(4):271-8
Oct-4: gatekeeper in the beginnings of mammalian development.
Pesce M, Scholer HR.
Laboratorio di Patologia Vascolare, Istituto Dermopatico dell' Immacolata, Rome, Italy.
The Oct-4 POU transcription factor is expressed in mouse totipotent embryonic stem and germ
cells. Differentiation of totipotent cells to somatic lineages occurs at the blastocyst stage and
during gastrulation, simultaneously with Oct-4 downregulation. Stem cell lines derived from the
inner cell mass and the epiblast of the mouse embryo express Oct-4 only if undifferentiated.
When embryonic stem cells are triggered to differentiate, Oct-4 is downregulated thus providing
a model for the early events linked to somatic differentiation in the developing embryo. In vivo
mutagenesis has shown that loss of Oct-4 at the blastocyst stage causes the cells of the inner cell
mass to differentiate into trophectoderm cells. Recent experiments indicate that an Oct-4
expression level of roughly 50%-150% of the endogenous amount in embryonic stem cells is
permissive for self-renewal and maintenance of totipotency. However, upregulation above these
levels causes stem cells to express genes involved in the lineage differentiation of primitive
endoderm. These novel advances along with latest findings on Oct-4-associated factors, target
genes, and dimerization ability, provide new insights into the understanding of the early steps
regulating mammalian embryogenesis.
Nat Genet 2000 Apr;24(4):372-6
Comment in:
Nat Genet. 2000 Apr;24(4):328-30
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. |
