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

ABSTRACT: Wnt/?-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/?-catenin functions in both self-renewal and differentiation in mouse epiblast stem cells. Stabilization and nuclear translocation of ?-catenin and its subsequent binding to T-cell factors induces differentiation. Conversely, retention of stabilized ?-catenin in the cytoplasm maintains self-renewal. Cytoplasmic retention of ?-catenin is effected by stabilization of Axin2, a downstream target of ?-catenin, or by genetic modifications to ?-catenin that prevent its nuclear translocation. We also find that human embryonic stem cell and mouse epiblast stem cell fates are regulated by ?-catenin through similar mechanisms. Our results elucidate a new role for ?-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.

SUBMITTER: Kim H 

PROVIDER: S-EPMC4183150 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature