Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells
- Author(s)
- Qian, H; Buza-Vidas, N; Hyland, CD; Jensen, CT; Antonchuk, J; Mansson, R; Thoren, LA; Ekblorn, M; Alexander, WS; Jacobsen, SEW;
- Details
- Publication Year 2007-12,Volume 1,Issue #6,Page 671-684
- Journal Title
- CELL STEM CELL
- Publication Type
- Journal Article
- Abstract
- The role of cytokines, in regulation of hematopoietic stem cells (HSCs) remains poorly understood. Herein we demonstrate that thrombopoietin (THPO) and its receptor, MPL, are critically involved in postnatal steady-state HSC maintenance, reflected in a 150-fold reduction of HSCs in adult Thpo(-1-) mice. Further, whereas THPO and MPL proved not required for fetal HSC expansion, HSC expansion posttransplantation was highly MPL and THPO dependent. The distinct role of THPO in postnatal HSC maintenance is accompanied by accelerated HSC cell-cycle kinetics in Thpo-1- mice and reduced expression of the cyclin-dependent kinase inhibitors p57(KiP2) and p19(INK4D) as well as multiple Hox transcription factors. Although also predicted to be an HSC viability factor, BCL2 failed to rescue the HSC deficiency of Thpo(-1-) mice. Thus, THPO regulates posttransplantation HSC expansion as well as the maintenance of adult quiescent HSCs, of critical importance to avoid postnatal HSC exhaustion.
- Publisher
- CELL PRESS
- Keywords
- RECEPTOR-DEFICIENT MICE; IN-VITRO; C-MPL; PROGENITOR CELLS; SELF-RENEWAL; LINEAGE COMMITMENT; GROWTH-FACTORS; EXPANSION; PROLIFERATION; VIVO
- Publisher's Version
- https://doi.org/10.1016/j.stem.2007.10.008
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- Refer to copyright notice on published article.
Creation Date: 2007-12-01 12:00:00