GSE113047
Activin/Smad2 and Wnt/ß-catenin upregulate HAS2 and ALDH3A2 to facilitate mesendoderm differentiation of human ESCs
Activin and Wnt signaling are necessary and sufficient for mesendoderm (ME) differentiation of human embryonic stem cells (hESCs). In this study, we report that during the Activin and Wnt induced ME differentiation, Activin/Smad2 induces decrease of the repressive histone modification H3K27me3 by promoting proteasome-dependent degradation of EZH2. As a result, recruitment of the forkhead protein FOXH1 on open chromatin regions integrates the signals of Activin/Smad2 and Wnt/ß-catenin to activate the expression of the ME genes including HAS2 and ALDH3A2. Knockdown of HAS2 and ALDH3A2 greatly attenuates ME differentiation. These findings unveil a pathway from extracellular signals to epigenetic modification-mediated gene activation during ME commitment. Overall design: H1 human embryonic stem cell cells were treated with 25ng/ml Activin A, 25ng/ml Wnt3a, or both (AW) for 6 h and then harvested for ATAC-seq.