Affiliation:
1. From the Sidney Kimmel Cancer Center and Department of Mathematics, University of California at San Diego, CA; and the Department of Microbiology and Immunology, University of Miami Medical School, FL.
Abstract
Most current theories assume that self-renewal and differentiation of hematolymphoid stem cells (HSCs) is randomly regulated by intrinsic and environmental influences. A direct corollary of these tenets is that self-renewal will continuously generate functionally heterogeneous daughter HSCs. Decisions about self-renewal versus commitment are made by individual, single HSCs and, thus, require examination on the clonal level. We followed the behavior of individual, clonally derived HSCs through long-term, serial repopulation experiments. These studies showed that daughter HSCs derived from individual clones were remarkably similar to each other in the extent and kinetics of repopulation. Moreover, daughter HSCs within a clone showed equivalent contributions to the myeloid or lymphoid lineages. Lineage contribution could be followed because of the discovery of a new subset of HSCs that gave rise stably to skewed ratios of myeloid and lymphoid cells. Overall, the data argue that self-renewal does not contribute to the heterogeneity of the adult HSC compartment. Rather, all HSCs in a clone follow a predetermined fate, consistent with the generation-age hypothesis. By extension, this suggests that the self-renewal and differentiation behavior of HSCs in adult bone marrow is more predetermined than previously thought.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference38 articles.
1. Clonal analysis of hematopoietic stem cell development in vivo.;Keller;Curr Top Microbiol Immunol.,1992
2. What we have learned from retroviral marking of hematopoietic stem cells.;Lemischka;Curr Top Microbiol. Immunol.,1992
3. Life span of multipotential hematopoietic stem cells in vivo.;Keller;J Exp Med.,1990
4. Clonal and systemic analysis of long-term hematopoiesis in the mouse.;Jordan;Genes Dev.,1990
5. Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function.;Spangrude;Blood.,1995
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