Promotion of self-renewal of embryonic stem cells by midkine

Abstract

To characterize the expression and function of midkine (MK) in an in vitro embryonic stem cell (ESC) culture system. To investigate the potential roles of MK, the expression of MK in ESCs was evaluated by RT-PCR and immunocytochemistry. The effects of MK on the self-renewal of ESCs were measured using alkaline phosphatase assays, immunocytochemistry, RT-PCR and colony-forming assays. The mechanism of the growth-promoting effect of MK in mESCs was assessed by cell cycle analysis and Western blot analysis. MK is expressed in mouse embryonic stem cells (mESCs), human embryonic stem cells (hESCs) and mouse embryonic fibroblasts (MEFs). MK promotes proliferation and self-renewal of mESCs both in feeder and feeder free culture systems. It also promotes self-renewal and proliferation of hESCs. Further study showed that MK promotes the growth of mESCs by inhibiting apoptosis while accelerating the progression toward the S phase, and enhances mESC self-renewal through PI3K/Akt signaling pathway. MK plays profound roles in ESCs. MK/PTPzeta signaling pathway is a novel pathway in the signal network maintaining pluripotency of ESCs. The results extend our knowledge on pluripotency control of ESCs and the relationship between ESCs and cancers.