2. Academic Validation
  3. Inhibition of β-catenin-TCF1 interaction delays differentiation of mouse embryonic stem cells

Inhibition of β-catenin-TCF1 interaction delays differentiation of mouse embryonic stem cells

  • J Cell Biol. 2015 Oct 12;211(1):39-51. doi: 10.1083/jcb.201503017.
Sujash S Chatterjee 1,  Abil Saj 2,  Tenzin Gocha 1,  Matthew Murphy 1,  Foster C Gonsalves 1,  Xiaoqian Zhang 2,  Penelope Hayward 3,  Betül Akgöl Oksuz 4,  Steven S Shen 4,  Aviv Madar 5,  Alfonso Martinez Arias 3,  Ramanuj DasGupta 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Pharmacology, New York University Cancer Institute, New York University Langone Medical Center, New York, NY 10016.
  • 2 Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672.
  • 3 Department of Genetics, University of Cambridge, Cambridge CB2 3EH, England, UK.
  • 4 Bioinformatics Core, New York University Langone Medical Center, New York, NY 10016.
  • 5 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853.
  • 6 Department of Biochemistry and Molecular Pharmacology, New York University Cancer Institute, New York University Langone Medical Center, New York, NY 10016 Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672.
PMID: 26459597 DOI: 10.1083/jcb.201503017
Abstract

The ability of mouse embryonic stem cells (mESCs) to self-renew or differentiate into various cell lineages is regulated by signaling pathways and a core pluripotency transcriptional network (PTN) comprising Nanog, Oct4, and Sox2. The Wnt/β-catenin pathway promotes pluripotency by alleviating T cell factor TCF3-mediated repression of the PTN. However, it has remained unclear how β-catenin's function as a transcriptional activator with TCF1 influences mESC fate. Here, we show that TCF1-mediated transcription is up-regulated in differentiating mESCs and that chemical inhibition of β-catenin/TCF1 interaction improves long-term self-renewal and enhances functional pluripotency. Genetic loss of TCF1 inhibited differentiation by delaying exit from pluripotency and conferred a transcriptional profile strikingly reminiscent of self-renewing mESCs with high Nanog expression. Together, our data suggest that β-catenin's function in regulating mESCs is highly context specific and that its interaction with TCF1 promotes differentiation, further highlighting the need for understanding how its individual protein-protein interactions drive stem cell fate.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-103705
    99.42%, Wnt 抑制剂
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