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First published online March 22, 2007
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2006-0611v1
25/7/1675    most recent
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Submitted on September 28, 2006
Accepted on March 14, 2007

Stem Cell Genetics and Genomics

Oct-4 expression in adult human differentiated cells challenges its role as a pure stem cell marker

Stefano Zangrossi 1, Mirko Marabese 2, Massimo Broggini 2, Rosaria Giordano 1, Marco D'Erasmo 1, Elisa Montelatici 1, Daniela Intini 3, Antonino Neri 3, Maurizio Pesce 4, Paolo Rebulla 1, Lorenza Lazzari 1*

1 Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
2 Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
3 Laboratory of Molecular Genetics and Gene Expression, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
4 Laboratory of Vascular Biology and Gene Therapy, Centro Cardiologico Monzino IRCCS, Milan, Italy

* To whom correspondence should be addressed. E-mail: cbbank{at}policlinico.mi.it.


   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 post-natal 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 RT-PCR (total RNA - Poly A+), Real Time-PCR, immunoprecipation and 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 questions 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.

Key Words. Oct-4, human peripheral cells, stem cell marker




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