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Thrombopoietin （TPO） is the primary cytokine responsible for regulating platelet production by stimulating the proliferation and differentiation of megakaryocytes, the bone marrow cells that produce platelets. TPO binds to the thrombopoietin receptor （TPO-R or c-Mpl） on hematopoietic stem cells （HSCs） and megakaryocyte progenitors, activating signaling pathways such as JAK2/STAT5, PI3K/AKT, and RAF-1/MAPK, which promote platelet production and maintain hematopoietic stem cell populations.
TPO and its receptor agonists （TPO-RAs） are widely used to treat immune thrombocytopenia （ITP）, chemotherapy-induced thrombocytopenia, and thrombocytopenia associated with chronic liver disease or myelodysplastic syndromes （MDS）37. Recombinant human TPO （rhTPO） and synthetic TPO-RAs （e.g., romiplostim, eltrombopag, avatrombopag） have shown efficacy in increasing platelet counts in clinical settings.