Thrombopoietin signaling is required for in vivo expansion of IL-11-responsive hematopoietic progenitor cells in the steady state
- Author(s)
- Scott, CL; Robb, L; Nandurkar, HH; Mansfield, R; Alexander, WS; Begley, CG;
- Details
- Publication Year 2001-02,Volume 29,Issue #2,Page 138-145
- Journal Title
- EXPERIMENTAL HEMATOLOGY
- Publication Type
- Journal Article
- Abstract
- Objective. mpl(-/-) mice have a profound defect in platelets and megakarycocytes and a defect in hematopoietic progenitor cells and stem cells. However, no specific subset of the progenitor/stem cell compartment has been shown to be particularly affected by this deficiency in mpl(-/-) mice. In this article, we identified a specific subset of hone marrow progenitor/stem cells that was altered in mpl(-/-) mice. Materials and Methods. In vitro and in vivo hematopoietic assays tr cre utilized to examine the response to interleulkin-11 in mice lacking the receptor 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, However, mpl(-/-) mice responded to IL-11 in vivo as evidenced by a rise in platelet 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 International Society for Experimental Hematology. Published by Elsevier Science Inc.
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- HUMAN MEGAKARYOCYTE GROWTH; MPL-DEFICIENT MICE; RECOMBINANT HUMAN INTERLEUKIN-11; EARLY ACTING CYTOKINES; PHASE-I TRIAL; STEM-CELL; C-MPL; BONE-MARROW; PLATELET PRODUCTION; GRANULOCYTE-MACROPHAGE
- Publisher's Version
- https://doi.org/10.1016/S0301-472X(00)00622-6
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- Refer to copyright notice on published article.
Creation Date: 2001-02-01 12:00:00