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

TitleThe WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells
Publication TypeJournal Article
Year of Publication2017
AuthorsHuggins I.J, Bos T., Gaylord O., Jessen C., Lonquich B., Puranen A., Richter J., Rossdam C., Brafman D., Gaasterland T., Willert K.
JournalNature Communications
Volume8
Date Published2017/10
Type of ArticleArticle
ISBN Number2041-1723
Accession NumberWOS:000413169000014
Keywordschromatin; colon-cancer; differentiation; expression; family; member; proteins; receptor fzd7; self-renewal; signaling pathway
Abstract

The WNT/beta-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.

DOI10.1038/s41467-017-01203-1
Short TitleNat. Commun.
Student Publication: 
No
Research Topics: 
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