title: Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner.
abstract: Stat3 is essential for mouse embryonic stem cell (mESC) self-renewal mediated by LIF/gp130 receptor signaling. Current understanding of Stat3-mediated ESC self-renewal mechanisms is very limited, and has heretofore been dominated by the view that Stat3 signaling functions in a binary "on/off" manner. Here, in contrast to this binary viewpoint, we demonstrate a contextual, rheostat-like mechanism for Stat3's function in mESCs. Activation and expression levels determine whether Stat3 functions in a self-renewal or a differentiation role in mESCs. We also show that Stat3 induces rapid differentiation of mESCs toward the trophectoderm (TE) lineage when its activation level exceeds certain thresholds. Stat3 induces this differentiation phenotype via induction of Tfap2c and its downstream target Cdx2. Our findings provide a novel concept in the realm of Stat3, self-renewal signaling, and pluripotent stem cell biology. Ultimately, this finding may facilitate the development of conditions for the establishment of authentic non-rodent ESCs.
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA Present address: Animal Biotechnology Interdisciplinary Group, Center for Veterinary Medicine, United States Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, USA.
authors.forename: Chih-I
authors.initials: CI
authors.lastname: Tai
authors.affiliation: Present address: Animal Biotechnology Interdisciplinary Group, Center for Veterinary Medicine, United States Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, USA.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Schulze
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA Present address: Animal Biotechnology Interdisciplinary Group, Center for Veterinary Medicine, United States Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, USA. qying@med.usc.edu.
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Ying
keywords: Embryonic stem cell; Pluripotency; Stat3