Niche regulation of hematopoietic stem cells in the endosteum: The role of thrombopoietinmpl signaling in the maintenance of quiescent Hematopoietic Stem Cells

Fumio Arai, Hiroki Yoshihara, Kentaro Hosokawa, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Toshio Suda

Research output: Chapter in Book/Report/Conference proceedingConference contribution

49 Citations (Scopus)

Abstract

During postnatal life, the bone marrow (BM) supports both the self-renewal and differentiation of hematopoietic stem cells (HSCs) in specialized niches. The interaction of HSCs with their niches also regulates the quiescence of HSCs. HSC quiescence is critical to ensure lifelong hematopoiesis and to protect the HSC pool from myelotoxic insult and premature exhaustion under conditions of hematopoietic stress. Here we identified long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, Mpl, as a quiescent population in adult BM. THPO was produced by bone-lining cells in the endosteum. Inhibition and stimulation of the THPOMpl pathway produced opposite effects on the quiescence of LT-HSC. Exogenous THPO transiently increased the quiescent LT-HSC population, such as side-population and pyronin Y-negative cells. In contrast, administration of an anti-Mpl neutralizing antibody, AMM2, suppressed the quiescence of LT-HSCs and enabled HSC engraftment without irradiation, indicating that inhibition of THPOMpl signaling reduces HSC-niche interactions. Moreover, it suggests that inhibiting the HSC-niche interaction could represent a novel technique for bone marrow transplantation without irradiation. Altogether, these data suggest that the THPOMpl signaling pathway is a novel niche component in the endosteum, and in the steady-state condition, this signaling pathway plays a critical role in the regulation of LT-HSCs in the osteoblastic niche.

Original languageEnglish
Title of host publicationHematopoietic Stem Cells VII
PublisherBlackwell Publishing Inc.
Pages36-46
Number of pages11
ISBN (Print)9781573317610
DOIs
Publication statusPublished - 2009 Jan 1

Publication series

NameAnnals of the New York Academy of Sciences
Volume1176
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Hematopoietic stem cell
  • Mpl
  • Osteoblastic cells
  • Quiescence
  • Thrombopoietin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Arai, F., Yoshihara, H., Hosokawa, K., Nakamura, Y., Gomei, Y., Iwasaki, H., & Suda, T. (2009). Niche regulation of hematopoietic stem cells in the endosteum: The role of thrombopoietinmpl signaling in the maintenance of quiescent Hematopoietic Stem Cells. In Hematopoietic Stem Cells VII (pp. 36-46). (Annals of the New York Academy of Sciences; Vol. 1176). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.04561.x