Dermatan-4--Sulfotransferase-1 Contributes to the Undifferentiated State of Mouse Embryonic Stem Cells.

Mouse embryonic stem cells (mESCs) have the properties of self-renewal and pluripotency. Various signals and growth factors maintain their undifferentiated state and also regulate their differentiation. Glycosaminoglycans are present on the cell surface and in the cell matrix as proteoglycans. Previously, we and other groups reported that the glycosaminoglycan heparan sulfate contributes to both maintenance of undifferentiated state and regulation of mESC differentiation. It has been shown that chondroitin sulfate is needed for pluripotency and differentiation of mESCs, while keratan sulfate is a known marker of human ESCs or induced pluripotent stem cells. We also found that DS promotes neuronal differentiation from mESCs and human neural stem cells; however, the function of DS in the maintenance of mESCs has not yet been revealed. Here, we investigated the role of DS in mESCs by knockdown (KD) or overexpression (O/E) of the () gene. We found that the activity of the ESC self-renewal marker alkaline phosphatase was reduced in KD mESCs, but, in contrast, increased in O/E mESCs. KD promoted endodermal differentiation, as indicated by an increase in expression. Conversely, expression was decreased by O/E. Wnt signaling, which is also involved in endodermal differentiation, was activated by KD and suppressed by O/E. Collectively, these results demonstrate that D4ST1 contributes to the undifferentiated state of mESCs. Our findings provide new insights into the function of DS in mESCs.