title: Modulation of β-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal.
abstract: Wnt/β-catenin signalling has a variety of roles in regulating stem cell fates. Its specific role in mouse epiblast stem cell self-renewal, however, remains poorly understood. Here we show that Wnt/β-catenin functions in both self-renewal and differentiation in mouse epiblast stem cells. Stabilization and nuclear translocation of β-catenin and its subsequent binding to T-cell factors induces differentiation. Conversely, retention of stabilized β-catenin in the cytoplasm maintains self-renewal. Cytoplasmic retention of β-catenin is effected by stabilization of Axin2, a downstream target of β-catenin, or by genetic modifications to β-catenin that prevent its nuclear translocation. We also find that human embryonic stem cell and mouse epiblast stem cell fates are regulated by β-catenin through similar mechanisms. Our results elucidate a new role for β-catenin in stem cell self-renewal that is independent of its transcriptional activity and will have broad implications in understanding the molecular regulation of stem cell fate.
authors.affiliation: 1] Department of Cell and Neurobiology, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA [2].
authors.forename: Hoon
authors.initials: H
authors.lastname: Kim
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Shoudong
authors.initials: S
authors.lastname: Ye
authors.forename: Chih-I
authors.initials: CI
authors.lastname: Tai
authors.forename: Xingliang
authors.initials: X
authors.lastname: Zhou
authors.forename: Hexin
authors.initials: H
authors.lastname: Yan
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Martin
authors.initials: M
authors.lastname: Pera
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Ying
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005855:Germ Layers / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D055550:Protein Stability; D051381:Rats; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; D051176:beta Catenin