Regulation of hematopoietic stem cells by their mature progeny
- Author(s)
- de Graaf, CA; Kauppi, M; Baldwin, T; Hyland, CD; Metcalf, D; Willson, TA; Carpinelli, MR; Smyth, GK; Alexander, WS; Hilton, DJ;
- Details
- Publication Year 2010-12-14,Volume 107,Issue #50,Page 21689-21694
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- 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/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.
- Publisher
- NATL ACAD SCIENCES
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003054/
- Publisher's Version
- https://doi.org/10.1073/pnas.1016166108
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-12-14 12:00:00
Last Modified: 2014-12-23 01:04:18