The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells
| Autor: | Karl Willert, Tomas Bos, Christina Jessen, Ian J. Huggins, Angeline Puranen, Brianna Lonquich, David A. Brafman, Terry Gaasterland, Charlotte Rossdam, Jenna Richter, Olivia Gaylord |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pluripotent Stem Cells Beta-catenin 1.1 Normal biological development and functioning Science General Physics and Astronomy Biology Regenerative Medicine General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences 0302 clinical medicine Underpinning research Wnt3A Protein Genetics Humans Stem Cell Research - Embryonic - Human lcsh:Science Induced pluripotent stem cell Wnt Signaling Pathway beta Catenin Regulation of gene expression Multidisciplinary Stem Cell Research - Induced Pluripotent Stem Cell Human Genome Wnt signaling pathway LRP6 LRP5 General Chemistry Stem Cell Research Embryonic stem cell Cell biology DNA-Binding Proteins 030104 developmental biology Gene Expression Regulation biology.protein lcsh:Q Stem Cell Research - Nonembryonic - Non-Human 030217 neurology & neurosurgery Biotechnology Transcription Factors |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017) Nature communications, vol 8, iss 1 |
| ISSN: | 2041-1723 |
| Popis: | 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. WNT/β-catenin signaling is an essential regulator of many developmental processes. Here, the authors provide evidence that activation of the WNT in human pluripotent stem cells leads to expression WNT target gene SP5, which then acts to diminish expression of active WNT target genes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|