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 Blood, 15 June 2007, Vol. 109, No. 12, pp. 5186-5190.
Prepublished online as a Blood First Edition Paper on March 8, 2007; DOI 10.1182/blood-2006-08-044503.

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HEMATOPOIESIS

Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones

Janis L. Abkowitz1, and Jing Chen1

1 Division of Hematology, Department of Medicine, University of Washington, Seattle, WA

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.


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