Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin.
Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin.
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DOI：
10.1084/jem.183.2.651
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发表时间：
1996-02-01
期刊：
影响因子：
--
通讯作者：
Moore MW
中科院分区：
文献类型：
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作者：
de Sauvage FJ;Carver-Moore K;Luoh SM;Ryan A;Dowd M;Eaton DL;Moore MW
血小板生成素(TPO)最近被克隆，并被证明通过激活细胞因子受体c-MPL来调节巨核细胞和血小板的产生。为了确定TPO是否是c-MPL的唯一配体和巨核细胞生成的主要调节因子，通过基因打靶的方法建立了TPO缺陷小鼠。TPO-/-小鼠的血小板和巨核细胞减少了80%，但所有其他类型的造血细胞水平正常。在杂合子小鼠中观察到的基因剂量效应表明，TPO基因是结构性表达的，循环中的TPO水平直接受血小板质量的调节。来自TPO-/-小鼠的骨髓减少了巨核系祖细胞的数量，并降低了存在的巨核细胞的倍性。这些结果表明，TPO单独是造血祖细胞增殖和分化为成熟巨核细胞的主要生理调节因子，但TPO对血小板生成的最后一步并不关键。
Thrombopoietin (TPO) has recently been cloned and shown to regulate megakaryocyte and platelet production by activating the cytokine receptor c-mpl. To determine whether TPO is the only ligand for c-mpl and the major regulator of megakaryocytopoiesis, TPO deficient mice were generated by gene targeting. TPO-/- mice have a >80% decrease in their platelets and megakaryocytes but have normal levels of all the other hematopoietic cell types. A gene dosage effect observed in heterozygous mice suggests that the TPO gene is constitutively expressed and that the circulating TPO level is directly regulated by the platelet mass. Bone marrow from TPO-/- mice have decreased numbers of megakaryocyte-committed progenitors as well as lower ploidy in the megakaryocytes that are present. These results demonstrate that TPO alone is the major physiological regulator of both proliferation and differentiation of hematopoietic progenitor cells into mature megakaryocytes but that TPO is not critical to the final step of platelet production.