Oct-4 Expression in Adult Human Differentiated Cells Challenges Its Role as a Pure Stem Cell Marker

Authors

  • Stefano Zangrossi,

    1. Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Mirko Marabese,

    1. Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy
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  • Massimo Broggini,

    1. Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy
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  • Rosaria Giordano,

    1. Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Marco D'Erasmo,

    1. Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Elisa Montelatici,

    1. Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Daniela Intini,

    1. Laboratory of Molecular Genetics and Gene Expression, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Antonino Neri,

    1. Laboratory of Molecular Genetics and Gene Expression, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Maurizio Pesce,

    1. Laboratory of Vascular Biology and Gene Therapy, Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
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  • Paolo Rebulla,

    1. Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Lorenza Lazzari D.Sc.

    Corresponding author
    1. Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
    • Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via F. Sforza 35, 20122 Milano, Italy. Telephone: +39 02 5503 4053; Fax: +39 02 5503 2796
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Abstract

The Oct-4 transcription factor, a member of the POU family that is also known as Oct-3 and Oct3/4, is expressed in totipotent embryonic stem cells (ES) and germ cells, and it has a unique role in development and in the determination of pluripotency. ES may have their postnatal counterpart in the adult stem cells, recently described in various mammalian tissues, and Oct-4 expression in putative stem cells purified from adult tissues has been considered a real marker of stemness. In this context, normal mature adult cells would not be expected to show Oct-4 expression. On the contrary, we demonstrated, using reverse transcription-polymerase chain reaction (PCR) (total RNA, Poly A+), real-time PCR, immunoprecipitation, Western blotting, band shift, and immunofluorescence, that human peripheral blood mononuclear cells, genetically stable and mainly terminally differentiated cells with well defined functions and a limited lifespan, express Oct-4. These observations raise the question as to whether the role of Oct-4 as a marker of pluripotency should be challenged. Our findings suggest that the presence of Oct-4 is not sufficient to define a cell as pluripotent, and that additional measures should be used to avoid misleading results in the case of an embryonic-specific gene with a large number of pseudogenes that may contribute to false identification of Oct-4 in adult stem cells. These unexpected findings may provide new insights into the role of Oct-4 in fully differentiated cells.

Disclosure of potential conflicts of interest is found at the end of this article.

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