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

Hoon Kim; Jun Wu; Shoudong Ye; Chih I. Tai; Xingliang Zhou; Hexin Yan; Ping Li; Martin Pera; Qi Long Ying

doi:10.1038/ncomms3403

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

Hoon Kim, Jun Wu, Shoudong Ye, Chih I. Tai, Xingliang Zhou, Hexin Yan, Ping Li, Martin Pera, Qi Long Ying

Research output: Contribution to journal › Article › peer-review

117 Scopus citations

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.

Original language	English (US)
Article number	2403
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3403
State	Published - Aug 29 2013
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms3403

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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.",

author = "Hoon Kim and Jun Wu and Shoudong Ye and Tai, {Chih I.} and Xingliang Zhou and Hexin Yan and Ping Li and Martin Pera and Ying, {Qi Long}",

note = "Funding Information: We thank C. Tong, D. Han and members of the USC Stem Cell Core for technical assistance; N. Wu and Y. Yan for blastocyst injections; Y. Chai for sharing the B6.129-Ctnnb1 mutant mice; R. Kemler for providing E-cadherin−/− mouse ESCs. C. Ashton and A.P. McMahon for critical reading of the manuscript. This work was supported by the California Institute for Regenerative Medicine (CIRM) New Faculty Award II (RN2-00938-1) and the CIRM Scientific Excellence through Exploration and Development (SEED) Grant (RS1-00327-1). Publisher Copyright: {\textcopyright} 2013 Macmillan Publishers Limited. All rights reserved.",

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AU - Kim, Hoon

AU - Wu, Jun

AU - Ye, Shoudong

AU - Tai, Chih I.

AU - Zhou, Xingliang

AU - Yan, Hexin

AU - Li, Ping

AU - Pera, Martin

AU - Ying, Qi Long

N1 - Funding Information: We thank C. Tong, D. Han and members of the USC Stem Cell Core for technical assistance; N. Wu and Y. Yan for blastocyst injections; Y. Chai for sharing the B6.129-Ctnnb1 mutant mice; R. Kemler for providing E-cadherin−/− mouse ESCs. C. Ashton and A.P. McMahon for critical reading of the manuscript. This work was supported by the California Institute for Regenerative Medicine (CIRM) New Faculty Award II (RN2-00938-1) and the CIRM Scientific Excellence through Exploration and Development (SEED) Grant (RS1-00327-1). Publisher Copyright: © 2013 Macmillan Publishers Limited. All rights reserved.

PY - 2013/8/29

Y1 - 2013/8/29

N2 - 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.

AB - 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.

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

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