First Author | Kim H | Year | 2013 |
Journal | Nat Commun | Volume | 4 |
Pages | 2403 | PubMed ID | 23985566 |
Mgi Jnum | J:354529 | Mgi Id | MGI:6834992 |
Doi | 10.1038/ncomms3403 | Citation | Kim H, et al. (2013) Modulation of beta-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal. Nat Commun 4:2403 |
abstractText | Wnt/beta-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/beta-catenin functions in both self-renewal and differentiation in mouse epiblast stem cells. Stabilization and nuclear translocation of beta-catenin and its subsequent binding to T-cell factors induces differentiation. Conversely, retention of stabilized beta-catenin in the cytoplasm maintains self-renewal. Cytoplasmic retention of beta-catenin is effected by stabilization of Axin2, a downstream target of beta-catenin, or by genetic modifications to beta-catenin that prevent its nuclear translocation. We also find that human embryonic stem cell and mouse epiblast stem cell fates are regulated by beta-catenin through similar mechanisms. Our results elucidate a new role for beta-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. |