Effect of dual-specificity protein phosphatase 5 on pluripotency maintenance and differentiation of mouse embryonic stem cells

The MAPK/Erk signaling pathway is considered as a key regulator of the pluripotency and differentiation of embryonic stem (ES) cells, while dual-specificity protein phosphatases (DUSPs) are negative regulators of MAPK. Although DUSPs are potential embryogenesis regulators, their functions in the regulation of ES cell differentiation have not been demonstrated. The present study revealed that Dusp5 was expressed in mouse ES (mES) cells and that its expression was correlated with the undifferentiated state of these cells. Exogenous Dusp5 expression enhanced mES cell clonogenicity and suppressed mES cell differentiation by maintaining Nanog expression via the inhibition of the Erk pathway. Following Dusp5 knockdown, Nanog and Oct4 expression was significantly attenuated and the Erk signaling pathway was activated. Additionally, EBs derived from Dusp5 knockdown mES cells (KDEBs) exhibited a weak adherence capability, very little outgrowth, and a reduction in the number of epithelial-like cells. The expression of Gata6 (an endodermal marker) and Flk1 and Twist1 (mesodermal markers) was inhibited in KDEBs, which indicated that Dusp5 influenced the differentiation of these germ layers during EB development. Collectively, this study suggested that Dusp5 plays an important role in the maintenance of pluripotency in mES cells, and that Dusp5 may be required for EB development.