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September 3, 1999Science486 citations

KDR Receptor: A Key Marker Defining Hematopoietic Stem Cells

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BZBenedikt ZieglerMVM ValtieriGAGraça Almeida‐Porada

Key Points

  • Identify a positive functional cell-surface marker capable of isolating pluripotent hematopoietic stem cells and distinguishing them from lineage-committed progenitor cells.
  • Analyzed human postnatal bone marrow, peripheral blood, and cord blood CD34+ cells for expression of VEGFR2 (KDR).
  • Quantified hematopoietic stem cell frequency using limiting dilution mouse xenograft models and 12-week long-term culture assays with and without VEGF supplementation.
  • Pluripotent hematopoietic stem cells were exclusively restricted to the CD34+KDR+ fraction (comprising 0.1% to 0.5% of CD34+ cells), whereas lineage-committed progenitors were CD34+KDR-.
  • Hematopoietic stem cell frequency within the CD34+KDR+ fraction was 20% in bone marrow by xenograft assay and 25% to 42% across tissues in 12-week cultures, rising to 53% to 63% with VEGF supplementation and exceeding 95% following growth factor starvation.

Abstract

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.

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Cite This Study

Ziegler et al. (1999) studied this question.

synapsesocial.com/papers/6a01c5cf60baf37e2cd8b9efhttps://doi.org/10.1126/science.285.5433.1553
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