Oct-4

Oct-4 is an abbreviation of Octamer-4. It is a homeodomain transcription factor of the POU family. This protein is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will actually cause differentiation of the cells.

Expression and function
Oct-4 is expressed in developing embryos throughout the preimplantation period. This transcription factor is initially active as a maternal factor in the oocyte but remains active in embryos throughout the preimplantation period. Oct-4 expression is associated with an undifferentiated phenotype and tumors. In fact gene knockdown of Oct-4 promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal.

Mouse embryos that are Oct-4-deficient or have low expression levels of Oct-4 fail to form the inner cell mass, lose pluripotency and differentiate into trophectoderm. Therefore, the level of Oct-4 expression in mice is vital for regulating pluripotency and early cell differentiation since one of its main functions is to keep the embryo from differentiating.

NCBI Information
Different alignment methods will give the different results about the orthologs. there are other orthologs from Drosophila(NCBI-GeneID: 38752),C.elegans(NCBI-GeneID: 172640) and so on. the two proteis are important in the development of animals.

Implications in Disease
Oct-4 has been implicated in tumorigenesis of adult germ cells. Ectopic expression of the factor in adult mice has been found to cause the formation of dysplastic lesions of the skin and intestine. The intestinal dysplasia resulted from an increase in progenitor cell population and the upregulation of β-catenin transcription through the inhibition of cellular differentiation.

Animal model
In 2000, Niwa et al used conditional expression and repression in murine embryonic stem (ES) cells to determine requirements for Oct-4 in the maintenance of developmental potency. Although transcriptional determination has usually been considered as a binary on-off control system, they found that the precise level of Oct-4 governs 3 distinct fates of ES cells. A less-than-2-fold increase in expression causes differentiation into primitive endoderm and mesoderm. In contrast, repression of Oct-4 induces loss of pluripotency and dedifferentiation to trophectoderm. Thus, a critical amount of Oct-4 is required to sustain stVentral veinlessem cell self-renewal, and up- or down regulation induces divergent developmental programs. Niwa et al suggested that their findings established a role for Oct-4 as a master regulator of pluripotency that controls lineage commitment and illustrated the sophistication of critical transcriptional regulators and the consequent importance of quantitative analyzes.

Although role of Oct-4 as a one of four essential pluripotent genes (namely, Oct-4, SOX2, c-Myc, and Klf4) for embryonic stem cells has been well-documented , several studies suggested role of these genes in sustaining self-renewal capacity of adult somatic stem cells (i.e. Stem cells from intestinal epithelium, bone marrow, retina, brain, liver, etc.). These genes are thought to be active in such adult stem cells in low quantity. However, Jaenisch at the Whitehead Institute in Cambridge, Massachusetts and his colleagues in Oct 2007 contradicted this hypothesis by documenting no role of Oct-4 in mouse somatic stem cell self-renewal. This study now demands further research to identify other factors involved in self-renewal capacity of adult stem cell.