Transforming growth factor-beta superfamily in mouse embryonic stem cell self-renewal

Embryonic stem (ES) cells are pluripotent cells that maintain the capability of undifferentiated self-renewal in culture. As mouse ES cells have the capacity to give rise to all the tissues of the body, they are an excellent developmental biology model system and a model for regenerative therapies. The extracellular cues and the intracellular signaling cascades that regulate ES cell self-renewal and cell-fate choices are complex and actively studied. Many developmental signaling pathways regulate the ES cell phenotype, and their intracellular programs interact to modulate the gene networks controlling ES cell pluripotency. This review focuses on the current understanding and outstanding questions of the roles of the transforming growth factor-beta-related signaling pathways in regulating pluripotency and differentiation of mouse ES cells. The complex dichotomic roles of bone morphogenetic protein signaling in maintaining the undifferentiated state and also inducing specific cell fates will be reviewed. The emerging roles of Nodal signaling in ES cell self-renewal will also be discussed.