Journal article
Regulation of hematopoietic stem cells by their mature progeny
CA De Graaf, M Kauppi, T Baldwin, CD Hyland, D Metcalf, TA Willson, MR Carpinelli, GK Smyth, WS Alexander, DJ Hilton
Proceedings of the National Academy of Sciences of the United States of America | Published : 2010
Abstract
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/Plt4mice show altered expressio..
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Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
The authors thank Jason Corbin for technical assistance and Kelly Trueman and Shauna Ross for animal husbandry. This work was supported by Program Grant 461219, fellowships (to D.J.H. and W.S.A.), Independent Research Institutes Support Scheme Grant 361646 from the Australian National Health and Medical Research Council of Australia, Grant R01 HL080019 from the National Heart, Lung, and Blood Institute, a fellowship from the Cancer Council, Victoria (to D. M.), an Australian Cancer Research Fund grant, and a Victorian State Government Operational Infrastructure Support grant and MuriGen Pty Ltd. C.A.d.G. was the recipient of an Australian Government Postgraduate Award, an Australian Stem Cell Centre Postgraduate Supplementary Scholarship, and the Sydney Parker Smith Postdoctoral Research Fellowship from the Cancer Council, Victoria.