Master stem cell transcription factors and signaling regulation

The present article reviews master stem cell transcription factors, their expression regulation network, and related signaling pathways with the aim of understanding the molecular mechanisms of pluripotent cell fate decisions. Oct4, Sox2, and Nanog are master transcription factors for maintenance of the undifferentiated state and self-renewal of embryonic stem cells (ESCs). In the mouse, they form a regulatory circuitry with coregulators, such as beta-catenin, Stat3, Myc, Klfs, Sall4, and Esrrb to control the expression of pluripotency-related genes including themselves. The threshold expression of Oct4, Sox2, and Nanog for sustaining ESC properties depends on the synergistic effects among Stat3, beta-catenin, and Smad signaling pathway under the specific conditions of the ESC cytoplasmic microenvironment. Some of the salient differences in human ESC signaling pathways affecting their fate commitment are highlighted.