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First published online March 22, 2007
Stem Cells Vol. 25 No. 7 July 2007, pp. 1675 -1680
doi:10.1634/stemcells.2006-0611; www.StemCells.com
© 2007 AlphaMed Press

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STEM CELL GENETICS AND GENOMICS

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

Stefano Zangrossia, Mirko Marabeseb, Massimo Brogginib, Rosaria Giordanoa, Marco D'Erasmoa, Elisa Montelaticia, Daniela Intinic, Antonino Neric, Maurizio Pesced, Paolo Rebullaa, Lorenza Lazzaria

aCell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy;
bLaboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy;
cLaboratory of Molecular Genetics and Gene Expression, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy;
dLaboratory of Vascular Biology and Gene Therapy, Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy

Key Words. Oct-4 • Human peripheral cells • Stem cell marker

Correspondence: Lorenza Lazzari, D.Sc., 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; e-mail: cbbank{at}policlinico.mi.it

Received September 28, 2006; accepted for publication March 14, 2007.
First published online in STEM CELLS EXPRESS   March 22, 2007.



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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