Thrombopoietin/MPL Signaling Regulates Hematopoietic Stem Cell Quiescence and Interaction with the Osteoblastic Niche

Hiroki Yoshihara, Fumio Arai, Kentaro Hosokawa, Tetsuya Hagiwara, Keiyo Takubo, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Sahoko Matsuoka, Kana Miyamoto, Hiroshi Miyazaki, Takao Takahashi, Toshio Suda

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457 Citations (Scopus)

Abstract

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 β1-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.

Original languageEnglish
Pages (from-to)685-697
Number of pages13
JournalCell stem cell
Volume1
Issue number6
DOIs
Publication statusPublished - 2007 Dec 13

Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Yoshihara, H., Arai, F., Hosokawa, K., Hagiwara, T., Takubo, K., Nakamura, Y., Gomei, Y., Iwasaki, H., Matsuoka, S., Miyamoto, K., Miyazaki, H., Takahashi, T., & Suda, T. (2007). Thrombopoietin/MPL Signaling Regulates Hematopoietic Stem Cell Quiescence and Interaction with the Osteoblastic Niche. Cell stem cell, 1(6), 685-697. https://doi.org/10.1016/j.stem.2007.10.020