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Oct-4
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==Pluripotency in embryo development== === Animal model === In 2000, Niwa et al. used conditional expression and repression in murine embryonic stem cells to determine requirements for Oct-4 in the maintenance of developmental potency.<ref name="pmid10742100"/> Although transcriptional determination has often 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. An increase in expression of less than 2-fold 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 stem cell self-renewal, and up- or down-regulation induces divergent developmental programs. Changes to Oct-4 levels do not independently promote differentiation, but are also controlled by levels of [[Sox2]]. A decrease in Sox2 accompanies increased levels of Oct-4 to promote a mesendodermal fate, with Oct-4 actively inhibiting ectodermal differentiation. Repressed Oct-4 levels that lead to ectodermal differentiation are accompanied by an increase in Sox2, which effectively inhibits mesendodermal differentiation.<ref name = "Thomson_2011">{{cite journal | vauthors = Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S | title = Pluripotency factors in embryonic stem cells regulate differentiation into germ layers | journal = Cell | volume = 145 | issue = 6 | pages = 875β89 | date = June 2011 | pmid = 21663792 | pmc = 5603300 | doi = 10.1016/j.cell.2011.05.017 }}</ref> 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. The transcription factors Oct-4, Sox2, and Nanog are part of a complex regulatory network, with Oct-4 and Sox2 being capable of directly regulating Nanog by binding to its promoter, and are essential for maintaining the self-renewing undifferentiated state of the inner cell mass of the blastocyst, [[embryonic stem cell]] lines<ref>Heurtier, V., Owens, N., Gonzalez, I. et al. The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells. Nat Commun 10, 1109 (2019). https://doi.org/10.1038/s41467-019-09041-z</ref> (which are cell lines derived from the inner cell mass), and induced pluripotent stem cells.<ref name=Rodda2005/> While differential up- and down-regulation of Oct-4 and Sox2 has been shown to promote differentiation, down-regulation of Nanog must occur for differentiation to proceed.<ref name = "Thomson_2011"/>
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