Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis

  title={Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis},
  author={Scott T. Avecilla and Koichi Hattori and Beate Heissig and Rafael E. Tejada and Francesca-Fang Liao and Koji Shido and David K. Jin and S{\'e}rgio Dias and Fan Zhang and Travis E. Hartman and Neil R. Hackett and Ronald G. Crystal and Larry D. Witte and Daniel J. Hicklin and Peter Bohlen and Dan L. Eaton and David C. Lyden and Fred de Sauvage and Shahin Rafii},
  journal={Nature Medicine},
The molecular pathways involved in the differentiation of hematopoietic progenitors are unknown. Here we report that chemokine-mediated interactions of megakaryocyte progenitors with sinusoidal bone marrow endothelial cells (BMECs) promote thrombopoietin (TPO)-independent platelet production. Megakaryocyte-active cytokines, including interleukin-6 (IL-6) and IL-11, did not induce platelet production in thrombocytopenic, TPO-deficient (Thpo−/−) or TPO receptor–deficient (Mpl−/−) mice. In… 

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The results indicate that low levels of TGF1 can modulate SDF-1 responsiveness of CD34 cells and thus may facilitate SDF–1–mediated retention and nurturing of stem/progenitor cells in bone marrow.



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Results suggest that SDF-1 directly promotes the proliferation of megakaryocytic progenitors in the presence of TPO, and in this way contributes to the favorable effects of the bone marrow microenvironment onmegakaryocyte development.

Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases.

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Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+ stem cells from bone-marrow microenvironment

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