National Centre for Cell Science, Pune, India.
SP Pune University, India.
FEBS Lett. 2022 Jul;596(13):1647-1660. doi: 10.1002/1873-3468.14341. Epub 2022 Apr 6.
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.
E-钙黏蛋白（CDH1）参与维持胚胎干细胞（ESCs）中的细胞间黏附。然而，其在细胞命运决定方面的功能在很大程度上尚不清楚。利用小鼠 ESCs（mESCs），我们证明 E-钙黏蛋白和β-连环蛋白在细胞膜上相互作用，并在细胞内内化后继续相互作用。Cdh1 mESCs 无法形成紧密的集落，分化过程中出现分化改变、标记物表达和多能性因子保留改变。有趣的是，Cdh1 mESCs 中β-连环蛋白水平显著降低。Cdh1 mESCs 的转录谱显示，β-连环蛋白靶基因子集的表达在细胞状态和 GSK3β 依赖性方式下发生显著改变。我们的研究结果暗示 E-钙黏蛋白在调节 ESCs 中β-连环蛋白活性方面发挥了迄今为止未知的作用。
