title: A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance.
abstract: 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.
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Livigni
authors.affiliation: The Danish Stem Cell Centre (DanStem), University of Copenhagen, 3B Blegdamsvej, 2200 Copenhagen, Denmark.
authors.forename: Hanna
authors.initials: H
authors.lastname: Peradziryi
authors.affiliation: Laboratory of Genetics, National Institute on Aging, NIH Biomedical Research Centre, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Sharov
authors.affiliation: Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Gloryn
authors.initials: G
authors.lastname: Chia
authors.affiliation: 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.
authors.forename: Fella
authors.initials: F
authors.lastname: Hammachi
authors.affiliation: 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.
authors.forename: Rosa Portero
authors.initials: RP
authors.lastname: Migueles
authors.affiliation: The Danish Stem Cell Centre (DanStem), University of Copenhagen, 3B Blegdamsvej, 2200 Copenhagen, Denmark.
authors.forename: Woranop
authors.initials: W
authors.lastname: Sukparangsi
authors.affiliation: School of Chemistry, Joseph Black Building, King's Buildings, the University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pernagallo
authors.affiliation: School of Chemistry, Joseph Black Building, King's Buildings, the University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bradley
authors.affiliation: Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nichols
authors.affiliation: Laboratory of Genetics, National Institute on Aging, NIH Biomedical Research Centre, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA; Department of Systems Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.
authors.forename: Minoru S H
authors.initials: MSH
authors.lastname: Ko
authors.affiliation: 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; The Danish Stem Cell Centre (DanStem), University of Copenhagen, 3B Blegdamsvej, 2200 Copenhagen, Denmark. Electronic address: joshua.brickman@sund.ku.dk.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Brickman
mesh_terms: D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004475:Ectoderm / Q000378:metabolism; D004625:Embryo, Nonmammalian; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D015820:Cadherins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D029867:Xenopus Proteins