H(2)S protects against fatal myelosuppression by promoting the generation of megakaryocytes/platelets

BACKGROUND: Our previous pilot studies aimed to examine the role of hydrogen sulfide (H(2)S) in the generation of endothelial progenitor cells led to an unexpected result, i.e., H(2)S promoted the differentiation of certain hematopoietic stem/progenitor cells in the bone marrow. This gave rise to an idea that H(2)S might promote hematopoiesis. METHODS: To test this idea, a mice model of myelosuppression and cultured fetal liver cells were used to examine the role of H(2)S in hematopoiesis. RESULTS: H(2)S promoted the generation of megakaryocytes, increased platelet levels, ameliorate entorrhagia, and improved survival. These H(2)S effects were blocked in both in vivo and in vitro models with thrombopoietin (TPO) receptor knockout mice (c-mpl(−/−) mice). In contrast, H(2)S promoted megakaryocytes/platelets generation in both in vivo and in vitro models with TPO knockout mice (TPO(−/−) mice). CONCLUSIONS: H(2)S is a novel promoter for megakaryopoiesis by acting on the TPO receptors but not TPO to generate megakaryocytes/platelets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0244-7) contains supplementary material, which is available to authorized users.