During mesenchymal stem cell (MSC) differentiation, both Wnt signaling and the development of a rigid cytoskeleton promote commitment to the osteoblastic over adipogenic lineage. -catenin  is thought to play a critical role in Wnt effects. We show that -catenin  was additive with cytoskeletal signals to prevent adipogenesis, and -catenin  knockdown promoted adipogenesis even when the actin cytoskeleton was depolymerized. -catenin  also prevented osteoblast commitment in a cytoskeletal-independent manner, with -catenin  knockdown enhancing lineage commitment. Chip-seq showed that -catenin associated with the promoter of EZH2, a key component of the PRC2 complex that governs genome methylation. Knocking down -catenin  lowered EZH2 levels and H3K27me3 at osteogenic loci. Further, when EZH2 was inhibited, -catenin s anti-differentiation effects were lost. These results indicate that regulating EZH2 activity is key to -catenin effects on MSC to preserve MSC multipotentiality. SOURCE: Andre,J,van Wijnen (vanwijnen.andre@mayo.edu) -  Mayo Clinic

Pluto Bioinformatics

GSE138980: RNA-sequencing and ChIP-sequencing in murine mesenchymal stem cells treated with Ezh2 inhibitor GSK126 or -catenin siRNA