KDR Receptor: A Key Marker Defining Hematopoietic Stem Cells

Science. 1999 Sep 3;285(5433):1553-8. doi: 10.1126/science.285.5433.1553.

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.

MeSH terms

  • Animals
  • Antigens, CD34 / analysis*
  • Bone Marrow Cells / cytology
  • Cell Lineage
  • Cell Separation
  • Cells, Cultured
  • Endothelial Growth Factors / pharmacology
  • Female
  • Fetal Blood / cytology
  • Fetus
  • Flow Cytometry
  • Hematopoiesis*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / chemistry
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Lymphokines / pharmacology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Phenotype
  • Pregnancy
  • Receptor Protein-Tyrosine Kinases / analysis*
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptors, Growth Factor / analysis*
  • Receptors, Growth Factor / physiology
  • Receptors, Vascular Endothelial Growth Factor
  • Sheep
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antigens, CD34
  • Endothelial Growth Factors
  • Lymphokines
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor