FORMATION OF PLURIPOTENT STEM-CELLS IN THE MAMMALIAN EMBRYO DEPENDS ON THE POU TRANSCRIPTION FACTOR OCT4

Oct4 is a mammalian POU transcription factor expressed by early embryo cells and germ cells. We report that the activity of Oct4 is essentia l for the identity of the pluripotential founder cell population in th e mammalian embryo. Oct4-deficient embryos develop to the blastocyst s tage, but the inner cell mass cells are not pluripotent. Instead, they are restricted to differentiation along the extraembryonic trophoblas t lineage. Furthermore, in the absence of a true inner cell mass, trop hoblast proliferation is not maintained in Oct4(-/-) embryos. Expansio n of trophoblast precursors is restored, however, by an Oct4 target ge ne product, fibroblast growth factor-4. Therefore, Oct4 also determine s paracrine growth factor signaling from stem cells to the trophectode rm.