Cell-cell adhesions in embryonic stem cells regulate the stability and transcriptional activity of β-catenin

FEBS Lett. 2022 Jul;596(13):1647-1660. doi: 10.1002/1873-3468.14341. Epub 2022 Apr 6.

Abstract

E-cadherin (CDH1) is involved in maintaining cell-cell adhesions in embryonic stem cells (ESCs). However, its function in the context of cell fate decisions is largely unknown. Using mouse ESCs (mESCs), we demonstrate that E-cadherin and β-catenin interact at the membrane and continue to do so upon internalization within the cell. Cdh1-/- mESCs failed to form tight colonies, with altered differentiation, marker expression and retention of pluripotency factors during differentiation. Interestingly, Cdh1-/- mESCs showed dramatically reduced β-catenin levels. Transcriptional profiling of Cdh1-/- mESCs displayed a significant alteration in the expression of a subset of β-catenin targets in a cell state- and GSK3β-dependent manner. Our findings hint at hitherto unknown roles played by E-cadherin in regulating the activity of β-catenin in ESCs.

Keywords: E-cadherin; cell adhesion; embryonic stem cells; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion / genetics
  • Cell Differentiation / genetics
  • Embryonic Stem Cells* / metabolism
  • Mice
  • Mouse Embryonic Stem Cells
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • Cadherins
  • beta Catenin