TY - JOUR
T1 - A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance
AU - Livigni, Alessandra
AU - Peradziryi, Hanna
AU - Sharov, Alexei A.
AU - Chia, Gloryn
AU - Hammachi, Fella
AU - Migueles, Rosa Portero
AU - Sukparangsi, Woranop
AU - Pernagallo, Salvatore
AU - Bradley, Mark
AU - Nichols, Jennifer
AU - Ko, Minoru S.H.
AU - Brickman, Joshua M.
N1 - Funding Information:
We thank Dawood Dudekula, Joe Mee, Lucy Jones, Yong Qian, Valeria Berno, Ron Wilkie, Marylin Thomson, Helen Henderson, Laure Plantard, and Gelo dela Cruz for technical assistance. We are grateful to H. Sive, M. Taira, H. Niwa, P. McCrea, I. Chambers, S. Lowell, H. Lickert, P. Tesar, and J. Chenoweth for plasmids and data sets. We thank Anne Grapin-Botton, Sally Lowell, and Adam Laing for critical reading of this manuscript. This work was supported by the Medical Research Council (MRC) (G0701428) and the Novo Nordisk Foundation (to J.M.B.) and by the Intramural Research Program of the NIH and the National Institute on Aging (Z01AG AG000656 and Z01AG000662) (to M.S.H.K.). J.M.B. was supported by an MRC Senior Non-Clinical Fellowship.
PY - 2013/11/18
Y1 - 2013/11/18
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cub.2013.09.048
DO - 10.1016/j.cub.2013.09.048
M3 - Article
C2 - 24210613
AN - SCOPUS:84889085264
SN - 0960-9822
VL - 23
SP - 2233
EP - 2244
JO - Current Biology
JF - Current Biology
IS - 22
ER -