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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2317-2321.
Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-06-2249.
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Submitted June 6, 2005
Accepted November 7, 2005
Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow
Alejandro B Balazs, Attila J Fabian, Charles T Esmon, and Richard C Mulligan*
Department of Genetics, Harvard Medical School, Boston, MA, USA
Division of Molecular Medicine, Children's Hospital, Boston, MA, USA
Cardiovascular Biology, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, and Departments of Pathology and Biochemistry & Molecular Biology, University of Oklahoma, Oklahoma City, OK, USA
Department of Genetics, Harvard Medical School, Boston, MA, USA; Division of Molecular Medicine, Children's Hospital, Boston, MA, USA
* Corresponding author; email: mulligan{at}receptor.med.harvard.edu.
The hematopoietic stem cell (HSC) is a unique cell type found in bone marrow which has the capacity for both self-renewal and differentiation into all blood lineages. The identification of genes expressed specifically in HSCs may help identify gene products vital to the control of self-renewal and/or differentiation, as well as antigens capable of forming the basis for improved methods of stem cell isolation. In previous studies, we identified a number of genes which appeared to be differentially expressed in murine bone marrow-derived hematopoietic stem cells, using microarray technology. We report here that one of those genes, encoding the murine endothelial protein C receptor (EPCR), is expressed at high levels within the bone marrow in hematopoietic stem cells. Bone marrow cells isolated on the basis of EPCR expression alone are highly enriched for hematopoietic reconstitution activity, showing levels of engraftment in vivo comparable to that of stem cells purified using the most effective conventional methods. Moreover, evaluation of cell populations first enriched for stem cell activity by conventional methods and subsequently fractionated on the basis of EPCR expression indicates that stem cell activity is always associated with EPCR-expressing cells. Based on our findings, we believe EPCR represents the first known marker that 'explicitly' identifies hematopoietic stem cells within murine bone marrow.

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