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  Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation

Wray, J., Kalkan, T., Gomez-Lopez, S., Eckardt, D., Cook, A., Kemler, R., & Smith, A. (2011). Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation. Nature Cell Biology, 13, 838-845.

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資料種別: 学術論文

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 作成者:
Wray, Jason, 著者
Kalkan, Tüzer, 著者
Gomez-Lopez, Sandra, 著者
Eckardt, Dominik1, 著者           
Cook, Andrew, 著者
Kemler, Rolf2, 著者           
Smith, Austin, 著者
所属:
1Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243651              
2Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243656              

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 要旨: Self-renewal of rodent embryonic stem cells is enhanced by partial inhibition of glycogen synthase kinase-3 (Gsk3; refs 1, 2). This effect has variously been attributed to stimulation of Wnt signalling by β-catenin, stabilization of Myc protein and global de-inhibition of anabolic processes. Here we demonstrate that β-catenin is not necessary for embryonic stem cell identity or expansion, but its absence eliminates the self-renewal response to Gsk3 inhibition. Responsiveness is fully restored by truncated β-catenin lacking the carboxy-terminal trans-activation domain. However, requirement for Gsk3 inhibition is dictated by expression of T-cell factor 3 (Tcf3) and mediated by direct interaction with β-catenin. Tcf3 local-izes to many pluripotency genes in embryonic stem cells. Our findings confirm that Tcf3 acts as a transcriptional repressor and reveal that β-catenin directly abrogates Tcf3 function. We conclude that Gsk3 inhibition stabilizes the embryonic stem cell state primarily by reducing repressive influence on the core pluripotency network.

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言語: eng - English
 日付: 2011-07
 出版の状態: 出版
 ページ: -
 出版情報: -
 目次: -
 査読: 査読あり
 識別子(DOI, ISBNなど): eDoc: 578906
 学位: -

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出版物 1

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出版物名: Nature Cell Biology
  出版物の別名 : Nat. Cell Biol.
種別: 学術雑誌
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出版社, 出版地: -
ページ: - 巻号: 13 通巻号: - 開始・終了ページ: 838 - 845 識別子(ISBN, ISSN, DOIなど): -