POU5F1 Isoforms Show Different Expression Patterns in Human Embryonic Stem Cells and Preimplantation Embryos

Authors

  • Greet Cauffman M.Sc.,

    Corresponding author
    1. Research Center Reproduction and Genetics, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Brussels, Belgium
    • Research Center Reproduction and Genetics, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Laarbeeklaan 101, 1090 Brussels, Belgium. Telephone: +32/24776690; Fax: +32/24776692
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  • Inge Liebaers,

    1. Research Center Reproduction and Genetics, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Brussels, Belgium
    2. Center for Medical Genetics, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Brussels, Belgium
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  • André Van Steirteghem,

    1. Research Center Reproduction and Genetics, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Brussels, Belgium
    2. Center for Reproductive Medicine, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Brussels, Belgium
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  • Hilde Van de Velde

    1. Research Center Reproduction and Genetics, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Brussels, Belgium
    2. Center for Reproductive Medicine, University Hospital and Medical School of the “Vrije Universiteit Brussel” (Free University of Brussels), Brussels, Belgium
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Abstract

The contribution of the POU domain, class 5, transcription factor-1 (POU5F1) in maintaining totipotency in human embryonic stem cells (hESCs) has been repeatedly proven. In humans, two isoforms are encoded: POU5F1_iA and POU5F1_iB. So far, no discrimination has been made between the isoforms in POU5F1 studies, and it is unknown which isoform contributes to the undifferentiated phenotype. Using immunocytochemistry, expression of POU5F1_iA and POU5F1_iB was examined in hESCs and all stages of human preimplantation development to look for differences in expression, biological activity, and relation to totipotency. POU5F1_iA and POU5F1_iB displayed different temporal and spatial expression patterns. During human preimplantation development, a significant POU5F1_iA expression was seen in all nuclei of compacted embryos and blastocysts and a clear POU5F1_iB expression was detected from the four-cell stage onwards in the cytoplasm of all cells. The cytoplasmic localization might imply no or other biological functions beyond transcription activation for POU5F1_iB. The stemness properties of POU5F1 can be assigned to POU5F1_iA because hESCs expressed POU5F1_iA but not POU5F1_iB. However, POU5F1_iA is not the appropriate marker to identify totipotent cells, because POU5F1_iA was also expressed in the nontotipotent trophectoderm and was not expressed in zygotes and early cleavage stage embryos, which are assumed to be totipotent. The expression pattern of POU5F1_iA may suggest that POU5F1_iA alone cannot sustain totipotency and that coexpression with other stemness factors might be the key to totipotency.

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