1 BasicStem NNF, The Danish Center for Stem Cell Research, Faculty of Health and Medical Sciences, Københavns Universitet2 Stem Cell and developmental Biology - early embryonic lineage specification Lab, The Danish Stem Cell Center, Faculty of Health and Medical Sciences, Københavns Universitet3 MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5 Little France Drive, University of Edinburgh, Edinburgh EH16 4UU, UK.4 unknown5 BasicStem NNF, The Danish Center for Stem Cell Research, Faculty of Health and Medical Sciences, Københavns Universitet6 Stem Cell and developmental Biology - early embryonic lineage specification Lab, The Danish Stem Cell Center, Faculty of Health and Medical Sciences, Københavns Universitet
BACKGROUND: The class V POU domain transcription factor Oct4 (Pou5f1) is a pivotal regulator of embryonic stem cell (ESC) self-renewal and reprogramming of somatic cells to induced pluripotent stem (iPS) cells. Oct4 is also an important evolutionarily conserved regulator of progenitor cell differentiation during embryonic development. RESULTS: Here we examine the function of Oct4 homologs in Xenopus embryos and compare this to the role of Oct4 in maintaining mammalian embryo-derived stem cells. Based on a combination of expression profiling of Oct4/POUV-depleted Xenopus embryos and in silico analysis of existing mammalian Oct4 target data sets, we defined a set of evolutionary-conserved Oct4/POUV targets. Most of these targets were regulators of cell adhesion. This is consistent with Oct4/POUV phenotypes observed in the adherens junctions in Xenopus ectoderm, mouse embryonic, and epiblast stem cells. A number of these targets could rescue both Oct4/POUV phenotypes in cellular adhesion and multipotent progenitor cell maintenance, whereas expression of cadherins on their own could only transiently support adhesion and block differentiation in both ESC and Xenopus embryos. CONCLUSIONS: Currently, the list of Oct4 transcriptional targets contains thousands of genes. Using evolutionary conservation, we identified a core set of functionally relevant factors that linked the maintenance of adhesion to Oct4/POUV. We found that the regulation of adhesion by the Oct4/POUV network occurred at both transcriptional and posttranslational levels and was required for pluripotency.
Current Biology : Cb, 2013, Vol 23, Issue 22, p. 2233-44