SMAD2介导Activin A信号促进人胚胎干细胞向限定性内胚层细胞诱导分化

In this paper, the study was done to confirm the affection of SMAD2 by which Activin A promoted the definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs). Western-blot analysis was carried out to detect the SMAD2 and p-SMAD2 expression levels on days 0, 6h, 12h, 1, 2, 3, 4 and 5 respectively, with the treatment of 100 ng/ml Activin A. Furthermore, hESCs treated with Activin A were detected with the mesoendoderm precursor related gene Brachyury and endodermal genes Sox17 genes expression changes after transfected with SMAD2 siRNA or expression plasmids. These results demonstrated that after Activin A＇s induction, Brachyury and Sox17 genes expressions were upregulated more quickly and dominantly. Coherent with these, the p-SMAD2 expression levels were also upregulated. SMAD RNAi or overexpression inhibited or promoted the induction of Activin A. These data indicates that SMAD2 is a key regulator of Activin A induction in DE differentiation of hESCs, which regulates developmental events through SMAD2 transcriptional modulators and promotes Brachyury and Sox17 proteins expression.