Do stem cells play dice?

Growth and differentiation signals mediated by different regions in the cytoplasmic domain of granulocyte-stimulating factor receptor. Touw IP: Distinct cytoplasmic regions of the human granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation.: The clonal proliferation of normal mouse hematopoietic cells: Enhancement and suppression by colony-stimulating factor combinations. of apoptosis allows differentiation and development of a multipotent hemopoietic cell line in the absence of added growth factors. AR: Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietin receptor c-Mpl. Blood 87:2162, 1996 28. Roberts AW, Metcalf D: Granulocyte colony-stimulating factor induces selective elevations of progenitor cells in the peripheral blood of mice. Broudy VC: Thrombopoietin expands erythroid, granulocyte-macro-phage, and megakaryocytic progenitor cells in normal and myelosup-pressed mice. Exp Hematol 24:265, 1996 30. Metcalf D: The cellular basis for enhancement interactions between stem cell factor and the colony stimulating factors. T HE DEBATE SURROUNDING the issue of whether or not hematopoietic stem cell commitment and differentiation are orchestrated in a cell-intrinsic or cell-extrinsic fashion is in many ways akin to the nature versus nurture debate that typifies discussions of human personal potentials. We have published data that could be interpreted as supporting both hypotheses. 1-3 Simply put, the question is this: is unilineage commitment the result of a cell-autonomous or internally driven program or rather is it the consequence of a cell responding to an external, ie, environmentally imposed, agenda? In the former case, stochastic processes are often invoked as instigators of lineage decisions. In instructive, or so-called deterministic schemes, cell-cell interactions or diffusible signals dictate cell fate decisions. Much attention has revolved around the role played by hematopoietic growth factors in this process: do they play an instructive, ie, a deterministic role, or are they simply permissive or selective, ie, allow the survival and proliferation of independently committed cells? Certainly, experiments using multipotent cell lines in vitro suggest that the addition of exogenous growth factors is essential for the survival and proliferation of the cells but not for the lineage commitment or subsequent differentiation and development into mature cells. 1,3 However, it has been argued that cultured cell lines, albeit with a normal karyotype, growth factor dependence, and ability to undergo multilineage differentiation, may not adequately reflect what happens with freshly isolated normal …