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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Version of Record online: 20 AUG 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 9, pages 1842–1851, September 2012
How to Cite
Hawkins, K., Mohamet, L., Ritson, S., Merry, C. L. R. and Ward, C. M. (2012), E-cadherin and, in Its Absence, N-cadherin Promotes Nanog Expression in Mouse Embryonic Stem Cells via STAT3 Phosphorylation. STEM CELLS, 30: 1842–1851. doi: 10.1002/stem.1148
Author contributions: K.H.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; L.M.: manuscript writing, provision of study material, and final approval of manuscript; S.R.: conception and design and manuscript writing; C.M.W.: conception and design, financial support, provision of study material, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; C.L.R.M.: conception and design and manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS June 13, 2012.
- Issue online: 20 AUG 2012
- Version of Record online: 20 AUG 2012
- Accepted manuscript online: 13 JUN 2012 02:39PM EST
- Manuscript Accepted: 24 MAY 2012
- Manuscript Received: 23 JAN 2012
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Engineering and Physical Sciences Research Council
- BBSRC PhD studentship
- Kruppel-like factor 4;
- Embryonic stem cells
We have recently shown that loss of E-cadherin in mouse embryonic stem cells (mESCs) results in significant alterations to both the transcriptome and hierarchy of pluripotency-associated signaling pathways. Here, we show that E-cadherin promotes kruppel-like factor 4 (Klf4) and Nanog transcript and protein expression in mESCs via STAT3 phosphorylation and that β-catenin, and its binding region in E-cadherin, is required for this function. To further investigate the role of E-cadherin in leukemia inhibitory factor (LIF)-dependent pluripotency, E-cadherin null (Ecad−/−) mESCs were cultured in LIF/bone morphogenetic protein supplemented medium. Under these conditions, Ecad−/− mESCs exhibited partial restoration of cell–cell contact and STAT3 phosphorylation and upregulated Klf4, Nanog, and N-cadherin transcripts and protein. Abrogation of N-cadherin using an inhibitory peptide caused loss of phospho STAT3, Klf4, and Nanog in these cells, demonstrating that N-cadherin supports LIF-dependent pluripotency in this context. We therefore identify a novel molecular mechanism linking E- and N-cadherin to the core circuitry of pluripotency in mESCs. This mechanism may explain the recently documented role of E-cadherin in efficient induced pluripotent stem cell reprogramming. Stem Cells2012;30:1842–1851