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Publication : Modulation of β-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal.

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.
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