Open AccessE‐cadherin and, in Its Absence, N‐cadherin Promotes Nanog Expression in Mouse Embryonic Stem Cells via STAT3 Phosphorylation
Author(s) -
Hawkins Kate,
Mohamet Lisa,
Ritson Sarah,
Merry Catherine L. R.,
Ward Christopher M.
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1148
Subject(s) - homeobox protein nanog , leukemia inhibitory factor , biology , rex1 , embryonic stem cell , nanog homeobox protein , microbiology and biotechnology , cadherin , reprogramming , induced pluripotent stem cell , phosphorylation , klf4 , stem cell , cell , genetics , gene
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