Regulation of hematopoietic stem cells by their mature progeny

被引：53

作者：

de Graaf, Carolyn A. ^{[2
,4
]}

Kauppi, Maria ^{[1
]}

Baldwin, Tracey ^{[2
]}

Hyland, Craig D. ^{[1
]}

Metcalf, Donald ^{[1
]}

Willson, Tracy A. ^{[2
]}

Carpinelli, Marina R. ^{[2
]}

Smyth, Gordon K. ^{[3
,5
]}

Alexander, Warren S. ^{[1
,4
]}

Hilton, Douglas J. ^{[2
,4
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, Parkville, Vic 3052, Australia

[2] Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic 3052, Australia

[3] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3052, Australia

[4] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[5] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 50期

基金：

英国医学研究理事会;

关键词：

C-MYB GENE; MEGAKARYOCYTIC LINEAGE; THROMBOPOIETIN LEVELS; CRITICAL ROLES; MPL(-/-) MICE; MPL; EXPRESSION; PLATELETS; THROMBOCYTOPENIA; RECEPTOR;

D O I：

10.1073/pnas.1016166108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation of megakaryocyte production and maintaining hematopoietic stem cell (HSC) quiescence. Mpl also controls circulating TPO concentration via receptor-mediated internalization and degradation. Here, we demonstrate that the megakaryocytosis and increased platelet mass in mice with mutations in the Myb or p300 genes causes reduced circulating TPO concentration and TPO starvation of the stem-cell compartment, which is exacerbated because these cells additionally exhibit impaired responsiveness to TPO. HSCs from Myb(Plt4/Plt4) mice show altered expression of TPO-responsive genes and, like HSCs from Tpo and Mpl mutant mice, exhibit increased cycling and a decline in the number of HSCs with age. These studies suggest that disorders of platelet number can have profound effects on the HSC compartment via effects on the feedback regulation of circulating TPO concentration.

引用

页码：21689 / 21694

页数：6

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