Potential of CD34 in the Regulation of Symmetrical and Asymmetrical Divisions by Hematopoietic Progenitor Cells

Abstract

The control of symmetric and asymmetric division in the hematopoietic stem/progenitor cell population is critically important for the regulation of blood cell production. Asymmetric divisions depend on cell polarization, which may be conferred by location and/or interaction with neighboring cells. In this study, we sought evidence for polarization in CD34+ cells, which interact by binding to one another. In these cells, surface molecules became redistributed by mechanisms that included transport by lipid rafts, and the interacting cells were able to communicate via gap junctions. These changes were accompanied by modulation of cell cycle regulating proteins (p16(Ink4a), p27(kip1), cyclins D, and the retinoblastoma pathway proteins) and a reduction in progenitor cell proliferation in vitro. These results are consistent with an increase in asymmetric cell division kinetics. Accordingly, we found that interaction between CD34+ cells influenced the plane of cell division in a way that suggests unequal sharing of Notch-1 between daughter cell progeny. We conclude that interaction between CD34+ cells may coordinate cell function and participate in the control of hematopoietic stem/progenitor cell division kinetics.