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Science 3 September 1999:
Vol. 285. no. 5433, pp. 1553 - 1558
DOI: 10.1126/science.285.5433.1553
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Reports

KDR Receptor: A Key Marker Defining Hematopoietic Stem Cells

B. L. Ziegler, *1 M. Valtieri, *23 G. Almeida Porada, 4 R. De Maria, 23 R. Müller, 1 B. Masella, 2 M. Gabbianelli, 3 I. Casella, 2 E. Pelosi, 3 T. Bock, 1 E. D. Zanjani, 4 C. Peschle 23dagger

Studies on pluripotent hematopoietic stem cells (HSCs) have been hindered by lack of a positive marker, comparable to the CD34 marker of hematopoietic progenitor cells (HPCs). In human postnatal hematopoietic tissues, 0.1 to 0.5% of CD34+ cells expressed vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR). Pluripotent HSCs were restricted to the CD34+KDR+ cell fraction. Conversely, lineage-committed HPCs were in the CD34+KDR- subset. On the basis of limiting dilution analysis, the HSC frequency in the CD34+KDR+ fraction was 20 percent in bone marrow (BM) by mouse xenograft assay and 25 to 42 percent in BM, peripheral blood, and cord blood by 12-week long-term culture (LTC) assay. The latter values rose to 53 to 63 percent in LTC supplemented with VEGF and to greater than 95 percent for the cell subfraction resistant to growth factor starvation. Thus, KDR is a positive functional marker defining stem cells and distinguishing them from progenitors.

1 Department of Hematology and Oncology, University of Tübingen, Otfried-Müller-Strasse 10, D-72076 Tübingen, Germany.
2 Kimmel Cancer Institute, Thomas Jefferson University, 233 South 10 Street, Philadelphia, PA 19107-5541, USA.
3 Department of Hematology and Oncology, Istituto Superiore di Sanità, V. le Regina Elena 299, 00161 Rome, Italy.
4 Department of Veterans Affairs, University of Nevada, Reno, NV 89520, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: cesare.peschle{at}mail.tju.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)