Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche

Cell Stem Cell. 2007 Dec 13;1(6):685-97. doi: 10.1016/j.stem.2007.10.020. Epub 2007 Nov 20.


Maintenance of hematopoietic stem cells (HSCs) depends on interaction with their niche. Here we show that the long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, MPL, are a quiescent population in adult bone marrow (BM) and are closely associated with THPO-producing osteoblastic cells. THPO/MPL signaling upregulated beta1-integrin and cyclin-dependent kinase inhibitors in HSCs. Furthermore, inhibition and stimulation of THPO/MPL pathway by treatments with anti-MPL neutralizing antibody, AMM2, and with THPO showed reciprocal regulation of quiescence of LT-HSC. AMM2 treatment reduced the number of quiescent LT-HSCs and allowed exogenous HSC engraftment without irradiation. By contrast, exogenous THPO transiently increased quiescent HSC population and subsequently induced HSC proliferation in vivo. Altogether, these observations suggest that THPO/MPL signaling plays a critical role of LT-HSC regulation in the osteoblastic niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Integrin beta1 / metabolism
  • Interphase
  • Mice
  • Osteoblasts / physiology*
  • Receptors, Thrombopoietin / metabolism*
  • Signal Transduction
  • Thrombopoietin / pharmacology
  • Thrombopoietin / physiology*
  • Up-Regulation


  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Integrin beta1
  • Receptors, Thrombopoietin
  • Thrombopoietin