Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones.
Three properties define hematopoietic stem cells (HSCs): their capacity for quiescence and long survival, their ability to self-renew, and their ability to give rise to a multilineage clone of differentiating and maturing blood cells. Although it is likely that different signals regulate these events, this has been difficult to dissect on a molecular level, since HSC division, their fate decisions, and the earliest differentiation events cannot be directly visualized. Our studies of c-Mpl, the cellular receptor for the cytokine thrombopoietin, suggest that c-Mpl does not control HSC numbers, as had been previously argued, but rather facilitates the early expansion of differentiating clones. These experiments provide a strategy to distinguish the actions of HSCs from earliest progenitor cells in vivo and demonstrate that a selective growth advantage at a level distal to HSC can result in a profound effect on multilineage hematopoiesis.
Abkowitz
Janis L
JL
Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195-7710, USA. janabk@u.washington.edu
Chen
Jing
J
D000818:Animals; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D053628:Receptors, Thrombopoietin / Q000032:analysis / Q000502:physiology*
C481270:Mpl protein, mouse; D053628:Receptors, Thrombopoietin