Thrombopoietin (TPO) is the cytokine that is chiefly responsible for megakaryocyte production but increasingly attention has turned to its role in maintaining hematopoietic stem cells (HSCs). HSCs are required to initiate the production of all mature hematopoietic cells, but this differentiation needs to be balanced against self-renewal and quiescence to maintain the stem cell pool throughout life. TPO has been shown to support HSC quiescence during adult hematopoiesis, with the loss of TPO signaling associated with bone marrow failure and thrombocytopenia. The binding of TPO to its receptor, c-Mpl, promotes the phosphorylation of cytoplasmic signaling proteins and activation of a number of cascades that control cellular proliferation, megakaryocyte development, and survival. Suppressors of cytokine signaling (SOCS), phosphatases, and other proteins, such as focal adhesion kinase and members of the Src family kinases can suppress TPO signaling.

TPO Signaling Pathway References