Physiological Regulation of Early and Late Stages of Megakaryocytopoiesis by Thrombopoietin

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1996 Feb 1

PMID 8627177

Citations 106

Authors

F J de Sauvage

S M Luoh

A Ryan

M Dowd

D L Eaton

M W Moore

Affiliations

Soon will be listed here.

Abstract

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.

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