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- Title
E-cadherin and, in Its Absence, N-cadherin Promotes Nanog Expression in Mouse Embryonic Stem Cells via STAT3 Phosphorylation.
- Authors
Hawkins, Kate; Mohamet, Lisa; Ritson, Sarah; Merry, Catherine L. R.; Ward, Christopher M.
- Abstract
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. S tem C ells 2012;30:1842-1851
- Subjects
GENE expression; CADHERINS; EMBRYONIC stem cells; PLURIPOTENT stem cells; PHOSPHORYLATION; MORPHOGENESIS; MOLECULAR genetics
- Publication
Stem Cells, 2012, Vol 30, Issue 9, p1842
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.1148