Article

Oct-4 controls cell-cycle progression of embryonic stem cells

Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea.
Biochemical Journal (Impact Factor: 4.78). 12/2009; 426(2):171-81. DOI: 10.1042/BJ20091439
Source: PubMed

ABSTRACT Mouse and human ES (embryonic stem) cells display unusual proliferative properties and can produce pluripotent stem cells indefinitely. Both processes might be important for maintaining the 'stemness' of ES cells; however, little is known about how the cell-cycle fate is regulated in ES cells. Oct-4, a master switch of pluripotency, plays an important role in maintaining the pluripotent state of ES cells and may prevent the expression of genes activated during differentiation. Using ZHBTc4 ES cells, we have investigated the effect of Oct-4 on ES cell-cycle control, and we found that Oct-4 down-regulation in ES cells inhibits proliferation by blocking cell-cycle progression in G0/G1. Deletion analysis of the functional domains of Oct-4 indicates that the overall integrity of the Oct-4 functional domains is important for the stimulation of S-phase entry. We also show in the present study that the p21 gene is a target for Oct-4 repression. Furthermore, p21 protein levels were repressed by Oct-4 and were induced by the down-regulation of Oct-4 in ZHBTc4 ES cells. Therefore the down-regulation of p21 by Oct-4 may contribute to the maintenance of ES cell proliferation.

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    • "Apart from embryonic stem cells, the Su Jin Kim et al. expression of Oct4 is also found in other cell types including mesenchymal stem cells (Fan et al., 2013), early embryonic tissues (DeVeale et al., 2013) and cancer cells (Li et al., 2012), although its roles and underlying mechanisms are still unclear. Recently, several reports have shown that the expression of Oct4 controls cell-cycle progression and enhances the proliferation of the cells for both embryonic stem cells (Lee et al., 2010) and other cell types (Li et al., 2012; DeVeale et al., 2013; Fan et al., 2013). "
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    • "NANOG directly activates transcription of CDK6 and CDC25A and therefore stimulates the beginning of the S-phase (Zhang et al., 2009b). Down-regulation of POU5F1 results in a decrease of cyclins and increase in CKI p21 in human mesenchymal stem cells and hESC, while up-regulation of POU5F1 correlates with an increase in specific CDK4 and CDC25A (Greco et al., 2007; Lee et al., 2010). Increased cell cycle duration, in particular the G1 phase, has been associated with the onset of neural differentiation in mESC and hESC (Lange et al., 2009; Borghese et al., 2010), e.g. "
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