Reversible expression of CD34 by murine hematopoietic stem cells.
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.
Sato
T
T
Departments of Pediatrics and Medicine, Medical University of South Carolina, Charleston, SC, USA.
Laver
J H
JH
Ogawa
M
M
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis*; D000950:Antigens, Ly / Q000032:analysis*; D015415:Biomarkers; D002453:Cell Cycle; D019070:Cell Lineage; D005472:Fluorouracil / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016130:Immunophenotyping; D017370:Interleukin-11 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011828:Radiation Chimera; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D000950:Antigens, Ly; D015415:Biomarkers; D017370:Interleukin-11; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens; D005472:Fluorouracil