TY - JOUR
T1 - Functional activity of murine CD34+ and CD34- hematopoietic stem cell populations
AU - Donnelly, D. Scott
AU - Zelterman, Daniel
AU - Sharkis, Saul
AU - Krause, Diane S.
N1 - Funding Information:
This work was supported in part by NIH grants RO1-DK53812 and R01 DK53037-01. Dr. Krause is a Leukemia Society of America Fellow. The authors wish to thank Terry Ashley, Maarit Jaarola, and Annemieke W. Plug for assistance with FISH; Barbara Degar and Ji-Yeon Lee for assistance with PCR; Michael Collector for assistance with elutriation; Rosemary Tercyak for administrative assistance; and Mark Shlomchik for review of this manuscript.
PY - 1999/5
Y1 - 1999/5
N2 - The transmembrane glycoprotein CD34 is expressed on human hematopoietic stem cells and committed progenitors in the bone marrow, and CD34-positive selection currently is used to isolate bone marrow repopulating cells in clinical transplantation protocols. Recently, CD34- hematopoietic stem cells were described in both humans and mice, and it was suggested that CD34+ murine bone marrow cells may lack long-term reconstituting ability. In this study, the long-term repopulating ability of CD34+Lin- vs CD34-Lin- cells was compared directly using syngeneic murine bone marrow transplantation. Highly purified populations of CD34+Lin- and CD34-Lin- cells each are able to reconstitute bone marrow, confirming that both populations contain hematopoietic stem cells; however, the number of hematopoietic stem cells in the CD34+Lin- fraction is approximately 100-fold greater than the number in the CD34-Lin- fraction. In competitive repopulation experiments, CD34+ stem cells are better able to engraft the bone marrow than are CD34- cells. CD34+Lin- cells provide both short- and long-term engraftment, but the CD34-Lin- cells are capable of only long-term engraftment. Ex vivo, the CD34+Lin- stem cells expand over 3 days in culture and maintain the ability to durably engraft animals in a serial transplant model. In contrast, when CD34-Lin- cells are cultured using the same conditions ex vivo, the cell number decreases, and the cells do not retain the ability to repopulate the bone marrow. Thus, the CD34+Lin- and CD34-Lin- cells constitute two functionally distinct populations that are capable of long-term bone marrow reconstitution.
AB - The transmembrane glycoprotein CD34 is expressed on human hematopoietic stem cells and committed progenitors in the bone marrow, and CD34-positive selection currently is used to isolate bone marrow repopulating cells in clinical transplantation protocols. Recently, CD34- hematopoietic stem cells were described in both humans and mice, and it was suggested that CD34+ murine bone marrow cells may lack long-term reconstituting ability. In this study, the long-term repopulating ability of CD34+Lin- vs CD34-Lin- cells was compared directly using syngeneic murine bone marrow transplantation. Highly purified populations of CD34+Lin- and CD34-Lin- cells each are able to reconstitute bone marrow, confirming that both populations contain hematopoietic stem cells; however, the number of hematopoietic stem cells in the CD34+Lin- fraction is approximately 100-fold greater than the number in the CD34-Lin- fraction. In competitive repopulation experiments, CD34+ stem cells are better able to engraft the bone marrow than are CD34- cells. CD34+Lin- cells provide both short- and long-term engraftment, but the CD34-Lin- cells are capable of only long-term engraftment. Ex vivo, the CD34+Lin- stem cells expand over 3 days in culture and maintain the ability to durably engraft animals in a serial transplant model. In contrast, when CD34-Lin- cells are cultured using the same conditions ex vivo, the cell number decreases, and the cells do not retain the ability to repopulate the bone marrow. Thus, the CD34+Lin- and CD34-Lin- cells constitute two functionally distinct populations that are capable of long-term bone marrow reconstitution.
KW - Bone marrow
KW - CD34
KW - Hematopoiesis
KW - Stem cell
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U2 - 10.1016/S0301-472X(99)00032-6
DO - 10.1016/S0301-472X(99)00032-6
M3 - Article
C2 - 10340393
AN - SCOPUS:0032897547
SN - 0301-472X
VL - 27
SP - 788
EP - 796
JO - Experimental Hematology
JF - Experimental Hematology
IS - 5
ER -