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

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.

Do extracellular vesicles have specific target cells?; Extracellular vesicle mediated embryo maternal communication

“…Proteins highly enriched in JAr EVs compared to HEK EVs were implicated in cell-cell adhesion (e.g., FBLN2, ITGB4, BCAM, CDH1, ITGB5) ( Chang et al, 2017 ; Meng et al, 2020 ; Ma et al, 2021 ; Bhattacharyya et al, 2022 ), early embryo development/differentiation (e.g., FOLR1, ERVW-1, CLDN6, EPCAM) ( Moriwaki et al, 2007 ; Nagao et al, 2009 ; Strandgaard et al, 2017 ; C.West et al, 2022 ), and endometrial receptivity (e.g., ENG, MMP2, MMP14) ( Arthur et al, 2000 ; Cabral-Pacheco et al, 2020 ) suggesting a potential role of trophoblastic EV protein cargo in the embryo implantation process.…”

“…Among the proteins highly enriched in trophoblast analogue JAr EVs, compared to HEK-293 EVs, we found proteins linked to embryo-maternal communication, implantation, and early embryo development. FBLN2, ITGB4, BCAM, ITGB5 are some of the proteins vital in cell-cell adhesion that mediate the interactions between embryonic and maternal tissues, facilitating attachment, invasion, and completion of successful implantation ( Chang et al, 2017 ; Meng et al, 2020 ; Ma et al, 2021 ; Bhattacharyya et al, 2022 ). During the peri-implantation phase, embryos undergo differentiation that is crucial for successful embryo implantation and further development.…”

BMP Stimulation Differentially Affects Phosphorylation and Protein Stability of β-Catenin in Breast Cancer Cell Lines

“…Similarly to these findings, BMP stimulation was only able to partially disrupt E-CADHERIN/β-CATENIN junctional complex formation and E-CADHERIN localization, whereas the total protein level of E-CADHERIN remained unchanged, and the migration ability of MCF7 cells was not affected. Bhattacharyya et al previously showed that inhibition of E-CADHERIN could disrupt localization and target gene expression of β-CATENIN in mouse embryonic stem cells [69]. Therefore, E-CADHERIN may not solely depend on β-CATENIN for the cadherin complex formation, though E-CADHERIN is critical for a proper membrane localization of β-CATENIN.…”