DUXO, a novel double homeobox transcription factor, is a regulator of the gastrula organizer in human embryonic stem cells

Human embryonic stem cells differentiate into gastrula organizer cells that express typical markers and induce secondary axes when injected into frog embryos. Here, we report that these human organizer cells express DUXO (DUX of the Organizer), a novel member of the double-homeobox (DUX) family of transcription factors, a group of genes unique to placental mammals. Both of DUXO's homeodomains share high similarity with those of Siamois and Twin, the initial inducers of the amphibian gastrula organizer. DUXO overexpression in human embryoid bodies induces organizer related genes, whereas its knock down hampers formation of the organizer and its derivatives. Finally, we show that DUXO regulates GOOSECOID, the canonical organizer marker, in a direct manner, suggesting that DUXO is a major regulator of human organizer formation. ► We analyzed previously isolated human organizer cells derived from hESCs. ► We identified DUXO — a novel gene highly expressed in the human organizer cells. ► DUXO regulates the expression of organizer related genes. ► We suggest that DUXO is the human equivalent of Siamois — the inducer of the amphibian organizer.