Author
Listed:
- Hoon Kim
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California)
- Jun Wu
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California
Present address: Salk Institute for Biological Studies, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA)
- Shoudong Ye
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California)
- Chih-I Tai
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California)
- Xingliang Zhou
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California)
- Hexin Yan
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California)
- Ping Li
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California)
- Martin Pera
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California
The Walter and Eliza Hall Institute of Medical Research, Florey Neurosciences Institutes, University of Melbourne)
- Qi-Long Ying
(Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California)
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.
Suggested Citation
Hoon Kim & Jun Wu & Shoudong Ye & Chih-I Tai & Xingliang Zhou & Hexin Yan & Ping Li & Martin Pera & Qi-Long Ying, 2013.
"Modulation of β-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal,"
Nature Communications, Nature, vol. 4(1), pages 1-11, December.
Handle:
RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3403
DOI: 10.1038/ncomms3403
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