Abstract

SummaryBackgroundThe 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.ResultsHere 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.ConclusionsCurrently, 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.

Highlights

  • In vertebrate development, lineage specification occurs progressively with time and utilizes pools of pluri- and multipotent progenitor cells with capacity to populate the different embryonic lineages

  • We found that our original depletion of POUV activity (PVD1, POUV-depleted 1; [9]) could be improved through the inclusion of additional morpholino antisense oligos (MO) that take into account potential pseudoalleles (PVD2, POUV-depleted 2; Table S1 available online)

  • We found that Xlim5/ Lhx5, Xcad2/Cdx1, Xlpou25 or mOct4, and to a limited extent E-cadherin rescued progenitor cell markers such as Brachyury and Bmp4 (Figure 4E)

Read more

Summary

Introduction

Lineage specification occurs progressively with time and utilizes pools of pluri- and multipotent progenitor cells with capacity to populate the different embryonic lineages. The self-renewal of pluripotent cells is regulated by defined extrinsic signals and coordinated by a gene regulatory network featuring the Class V POU transcription factor Oct4 [2, 3]. Oct is the central transcription factor in the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) [4, 5]. In vitro Oct has been shown to function as both an activator and repressor of gene transcription, but activation of Oct targets is sufficient to block differentiation and induce reprogramming [6]. To understand the role of Oct4/ POUV in maintaining pluripotency and supporting embryonic development, it is essential to decipher the function of the network activated by Oct and its homologs

Results
Discussion
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.