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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 26 OCT 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 10, pages 1794–1804, October 2010
How to Cite
Wagner, R. T., Xu, X., Yi, F., Merrill, B. J. and Cooney, A. J. (2010), Canonical Wnt/β-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression. STEM CELLS, 28: 1794–1804. doi: 10.1002/stem.502
Author contributions: R.T.W.: experimental design and execution, and wrote the manuscript; X.X.: isolated KO ES cell lines; F.Y.: experimental execution; B.J.M.: experimental, design; A.J.C.: experimental design, manuscript editing and funding.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS August 23, 2010.
- Issue published online: 26 OCT 2010
- Article first published online: 26 OCT 2010
- Accepted manuscript online: 23 AUG 2010 12:00AM EST
- Manuscript Accepted: 10 AUG 2010
- Manuscript Received: 1 MAR 2010
- ES cells;
Delineating the signaling pathways that underlie ESC pluripotency is paramount for development of ESC applications in both the research and clinical settings. In culture pluripotency is maintained by leukemia inhibitory factor (LIF) stimulation of two separate signaling axes: Stat3/Klf4/Sox2 and PI3K/Tbx3/Nanog, which converge in the regulation of Oct4 expression. However, LIF signaling is not required in vivo for self-renewal, thus alternate signaling axes likely mediate these pathways. Additional factors that promote pluripotency gene expression have been identified, including the direct regulation of Oct4 by liver receptor homolog-1 (Lrh-1) and β-catenin regulation of Nanog. Here, we present genetic, molecular, and pharmacological studies identifying a signaling axis in which β-catenin promotes pluripotency gene expression in an Lrh-1-dependent manner. Furthermore, Lrh-1 was identified as a novel β-catenin target gene, and Lrh-1 regulation is required for maintaining proper levels of Oct4, Nanog, and Tbx3. Elucidation of this pathway provides an alternate mechanism by which the primary pluripotency axis may be regulated in vivo and may pave the way for small molecule applications to manipulate pluripotency or improve the efficiency of somatic cell reprogramming. STEM CELLS 2010;28:1794–1804