Canonical Wnt/β-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression
| العنوان: | Canonical Wnt/β-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression |
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| المؤلفون: | Fei Yi, Ryan T. Wagner, Austin J. Cooney, Bradley J. Merrill, Xueping Xu |
| المصدر: | Stem Cells (Dayton, Ohio) |
| بيانات النشر: | Wiley Subscription Services, Inc., A Wiley Company, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Homeobox protein NANOG, Pluripotency, Male, Chromatin Immunoprecipitation, Rex1, Cellular differentiation, Blotting, Western, Fluorescent Antibody Technique, Receptors, Cytoplasmic and Nuclear, Oct4, Biology, Leukemia Inhibitory Factor, Embryonic Stem Cells/Induced Pluripotent Stem Cells, Cell Line, 03 medical and health sciences, Kruppel-Like Factor 4, Mice, 0302 clinical medicine, SOX2, Animals, reproductive and urinary physiology, Embryonic Stem Cells, beta Catenin, 030304 developmental biology, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Liver receptor homolog-1, Wnt signaling pathway, Cell Differentiation, Cell Biology, β-catenin, ES cells, Lrh-1, 030220 oncology & carcinogenesis, embryonic structures, Cancer research, Molecular Medicine, Female, Signal transduction, biological phenomena, cell phenomena, and immunity, Leukemia inhibitory factor, Octamer Transcription Factor-3, Developmental Biology |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1549-4918 1066-5099 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d93e6b25ab04f9ff0d52003a5e9d94f3 http://europepmc.org/articles/PMC2996860 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d93e6b25ab04f9ff0d52003a5e9d94f3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15494918 10665099 |
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