Thrombopoietin signaling is required for in vivo expansion of IL-11-responsive hematopoietic progenitor cells in the steady state

Objective. mpl(-/-) mice have a profound defect in platelets and megakaryco cytes and a defect in hematopoietic progenitor cells and stem cells. Howeve r, no specific subset of the progenitor/stem cell compartment has been show n to be particularly affected by this deficiency in mpl(-/-) mice. In this article, we identified a specific subset of hone marrow progenitor/stem cel ls that was altered in mpl(-/-) mice. Materials and Methods. In vitro and in vivo hematopoietic assays tr cre uti lized to examine the response to interleulkin-11 in mice lacking the recept or for thrombopoietin (TPO) (mpl(-/-) mice). Results. The interleukin (IL)-11-responsive subset of progenitor cells was not detected in clonal cultures of bone marrow cells from mpl(-/-) mice, Ho wever, mpl(-/-) mice responded to IL-11 in vivo as evidenced by a rise in p latelet count and an increase in spleen weight. Experiments were performed to address this paradox: administration of 5-fluorouracil with consequent " expansion" of early hematopoietic cells resulted in the appearance of IL-11 -responsive cells in mpl(-/-) mice when assayed in in vitro cultures, Conclusion. Thus, although mpl(-/-) mice hare the capacity to produce IL-11 -responsive progenitor cells, under steady state conditions their expansion is dependent on TPO. This is the first evidence that a specific subset of bone marrow progenitor/stem cells is altered in mpl(-/-) mice. (C) 2001 Int ernational Society for Experimental Hematology. Published by Elsevier Scien ce Inc.