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XB-ART-47788
Curr Biol November 18, 2013; 23 (22): 2233-2244.

A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance.

Livigni A , Peradziryi H , Sharov AA , Chia G , Hammachi F , Migueles RP , Sukparangsi W , Pernagallo S , Bradley M , Nichols J , Ko MSH , Brickman JM .


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.

PubMed ID: 24210613
PMC ID: PMC4228055
Article link: Curr Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actl6a bmp4 cdh1 cdx2 ctnnd1 fn1 lhx1 lhx5 not odc1 pou5f3.1 pou5f3.2 pou5f3.3 sall1 tbp tbxt tdgf1.1 tdgf1.2 tdgf1.3
Antibodies: Cdh1 Ab1 Cdh1 Ab7 Cdh3 Ab1 Ctnnb1 Ab7 Ctnnb1 Ab8 Ctnnd1 Ab1 FLAG Ab1 HA Ab5 Pou5f3.1 Ab1 Tubb3 Ab1
Morpholinos: pou5f3.1 MO2 pou5f3.2 MO1 pou5f3.2 MO3 pou5f3.3 MO2 pou5f3.3 MO3

GEO Series: GSE47578: NCBI

Article Images: [+] show captions
References [+] :
Banaszynski, A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. 2006, Pubmed