ERG1 plays an essential role in rat cardiomyocyte fate decision by mediating AKT signaling

ERG1 binds with Integrin β1 to activate the AKT pathway by recruiting and phosphorylating PI3K p85 and FAK, which promotes rat cardiomyocyte differentiation through mediating phosphorylation of GSK3β to upregulate the expression of both β‐catenin and Gata4, and meanwhile phosphorylating IKKβ to promote nuclear translo cation of nuclear factor‐κB for the inhibition of cell apoptosis. AbstractERG1, a potassium ion channel, is essential for cardiac action potential repolarization phase. However, the role of ERG1 for normal development of the heart is poorly understood. Using the rat embryonic stem cells (rESCs) model, we show that ERG1 is crucial in cardiomyocyte lineage commitment via interactions with Integrin β1. In the mesoderm phase of rESCs, the interaction of ERG1 with Integrin β1 can activate the AKT pathway by recruiting and phosphorylating PI3K p85 and focal adhesion kinase (FAK) to further phosphorylate AKT. Activation of AKT pathway promotes cardiomyocyte differentiation through two different mechanisms, (a) through phosphorylation of GSK3β to upregulate the expression levels of β‐catenin and Gata4; (b) through promotion of nuclear translocation of nuclear factor‐κB by phosphorylating IKKβ to inhibit cell apoptosis, which occurs due to increased Bcl2 expression. Our study provide s solid evidence for a novel role of ERG1 on differentiation of rESCs into cardiomyocytes.

Source: Stem Cells - February 8, 2021 Category: Stem Cells Authors: Duo Wang, Chang Liu, Huan Liu, Yilei Meng, Fang Lin, Yanqiong Gu, Hanrui Wang, Mengyue Shang, Chang Tong, Agapios Sachinidis, Qilong Ying, Li Li, Luying Peng Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research