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Embryonic stem cells (ESCs) are characterized by their ability of unlimited self-renewal in vitro and pluripotent developmental potential, which endows them with great values in basic research and future clinical application. However, realization of full potential of ESCs is dependent on the elucidation of molecular mechanisms governing ESCs, among which signaling pathways play critical roles. A great deal of efforts has been made in the past decades to understand what and how signaling pathways contribute to the establishment and maintenance of pluripotency. In this review, we discuss signaling networks in both mouse and human ESCs, focusing on signals involved in the control of self-renewal and differentiation. In addition, the modulation of signaling pathways by pluripotency-associated transcription factors is also briefly summarized. [ABSTRACT FROM AUTHOR]