Reversible expression of CD34 by murine hematopoietic stem cells

Blood. 1999 Oct 15;94(8):2548-54.


We used a mouse transplantation model to address the recent controversy about CD34 expression by hematopoietic stem cells. Cells from Ly-5.1 C57BL/6 mice were used as donor cells and Ly-5.2 mice were the recipients. The test cells were transplanted together with compromised marrow cells of Ly-5.2 mice. First, we confirmed that the majority of the stem cells with long-term engraftment capabilities of normal adult mice are CD34(-). We then observed that, after the injection of 150 mg/kg 5-fluorouracil (5-FU), stem cells may be found in both CD34(-) and CD34(+) cell populations. These results indicated that activated stem cells express CD34. We tested this hypothesis also by using in vitro expansion with interleukin-11 and steel factor of lineage(-) c-kit(+) Sca-1(+) CD34(-) bone marrow cells of normal mice. When the cells expanded for 1 week were separated into CD34(-) and CD34(+) cell populations and tested for their engraftment capabilities, only CD34(+) cells were capable of 2 to 5 months of engraftment. Finally, we tested reversion of CD34(+) stem cells to CD34(-) state. We transplanted Ly-5.1 CD34(+) post-5-FU marrow cells into Ly-5.2 primary recipients and, after the marrow achieved steady state, tested the Ly-5.1 cells of the primary recipients for their engraftment capabilities in Ly-5.2 secondary recipients. The majority of the Ly-5.1 stem cells with long-term engraftment capability were in the CD34(-) cell fraction, indicating the reversion of CD34(+) to CD34(-) stem cells. These observations clearly demonstrated that CD34 expression reflects the activation state of hematopoietic stem cells and that this is reversible.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD34 / biosynthesis*
  • Antigens, Ly / analysis*
  • Biomarkers
  • Cell Cycle
  • Cell Lineage
  • Fluorouracil / pharmacology
  • Gene Expression Regulation / drug effects
  • Graft Survival
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism*
  • Immunophenotyping
  • Interleukin-11 / pharmacology
  • Leukocyte Common Antigens / analysis
  • Membrane Proteins / analysis
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-kit / analysis
  • Radiation Chimera
  • Stem Cell Factor / pharmacology


  • Antigens, CD34
  • Antigens, Ly
  • Biomarkers
  • Interleukin-11
  • Ly6a protein, mouse
  • Membrane Proteins
  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit
  • Leukocyte Common Antigens
  • Fluorouracil