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The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells

Author

Listed:
  • Ian J. Huggins

    (University of California San Diego)

  • Tomas Bos

    (University of California San Diego)

  • Olivia Gaylord

    (University of California San Diego)

  • Christina Jessen

    (University of California San Diego)

  • Brianna Lonquich

    (University of California San Diego)

  • Angeline Puranen

    (University of California San Diego)

  • Jenna Richter

    (University of California San Diego)

  • Charlotte Rossdam

    (University of California San Diego)

  • David Brafman

    (Arizona State University)

  • Terry Gaasterland

    (University of California San Diego and Scripps Institution of Oceanography, Scripps Genome Center)

  • Karl Willert

    (University of California San Diego)

Abstract

The WNT/β-catenin signaling pathway is a prominent player in many developmental processes, including gastrulation, anterior–posterior axis specification, organ and tissue development, and homeostasis. Here, we use human pluripotent stem cells (hPSCs) to study the dynamics of the transcriptional response to exogenous activation of the WNT pathway. We describe a mechanism involving the WNT target gene SP5 that leads to termination of the transcriptional program initiated by WNT signaling. Integration of gene expression profiles of wild-type and SP5 mutant cells with genome-wide SP5 binding events reveals that SP5 acts to diminish expression of genes previously activated by the WNT pathway. Furthermore, we show that activation of SP5 by WNT signaling is most robust in cells with developmental potential, such as stem cells. These findings indicate a mechanism by which the developmental WNT signaling pathway reins in expression of transcriptional programs.

Suggested Citation

  • Ian J. Huggins & Tomas Bos & Olivia Gaylord & Christina Jessen & Brianna Lonquich & Angeline Puranen & Jenna Richter & Charlotte Rossdam & David Brafman & Terry Gaasterland & Karl Willert, 2017. "The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01203-1
    DOI: 10.1038/s41467-017-01203-1
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