TY - JOUR
T1 - The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells
AU - Huggins, Ian J.
AU - Bos, Tomas
AU - Gaylord, Olivia
AU - Jessen, Christina
AU - Lonquich, Brianna
AU - Puranen, Angeline
AU - Richter, Jenna
AU - Rossdam, Charlotte
AU - Brafman, David
AU - Gaasterland, Terry
AU - Willert, Karl
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031904865&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031904865&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01203-1
DO - 10.1038/s41467-017-01203-1
M3 - Article
C2 - 29044119
AN - SCOPUS:85031904865
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1034
ER -
