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 megakaryocytes 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 bone marrow progenitor/stem cells that was altered in mpl−/− mice. Materials and Methods In vitro and in vivo hematopoietic assays were utilized to examine the response to interleukin-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 have 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.