E-cadherin and, in its absence, N-cadherin promotes Nanog expression in mouse embryonic stem cells via STAT3 phosphorylation

Stem Cells. 2012 Sep;30(9):1842-51. doi: 10.1002/stem.1148.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cell Differentiation
  • Cell Growth Processes / physiology
  • Cells, Cultured
  • Embryonic Stem Cells / metabolism*
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / metabolism
  • Induced Pluripotent Stem Cells
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Nanog Homeobox Protein
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Transfection

Substances

  • Cadherins
  • GKLF protein
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • STAT3 Transcription Factor
  • Stat3 protein, mouse