Kyushu University Academic Staff Educational and Research Activities Database
List of Reports
Fumio Arai Last modified date:2019.06.27

Professor / Department of Stem Cell Biology and Medicine / Department of Stem Cell Biology and Medicine / Faculty of Medical Sciences


Reports
1. Fumio Arai, Hiroki Yoshihara, Hosokawa Kentaro, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Toshio Suda, Niche Regulation of Hematopoietic Stem Cells in the Endosteum The Role of Thrombopoietin/Mp1 Signaling in the Maintenance of Quiescent Hematopoietic Stem Cells, ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, HEMATOPOIETIC STEM CELLS VII, BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND, 巻: 1176 ページ: 36-46, 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, Mp1, as a quiescent population in adult BM. THPO was produced by bone-lining cells in the endosteum. Inhibition and stimulation of the THPO/Mp1 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-Mp1 neutralizing antibody, AMM2, suppressed the quiescence of LT-HSCs and enabled HSC engraftment without irradiation, indicating that inhibition of THPO/Mp1 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 THPO/Mp1 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.
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