All-trans retinoic acid and basic fibroblast growth factor synergistically direct pluripotent human embryonic stem cells to extraembryonic lineages

► hESCs were treated with retinoic acid (RA) and microarray studies were performed. ► RA modulates key signaling pathways such as WNT and TGF-β signaling. ► RA induces extraembryonic differentiation and increased the gonadotropin formation. ► RA bypasses the self-renewal effects of FGF-2 inducing extraembryonic differentiation. ► RA induces trophectodermal genes and hypermethylation of extraembryonic genes.