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Yoshihara, Hiroki; Arai, Fumio; Hosokawa, Kentaro; Hagiwara, Tetsuya; Takubo, Keiyo; Nakamura, Yuka; Gomei, Yumiko; Iwasaki, Hiroko; Matsuoka, Sahoko; Miyamoto, Kana; Miyazaki, Hiroshi; Takahashi, Takao; Suda, Toshio
Cell stem cell, 12/2007, Letnik: 1, Številka: 6Journal Article
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.
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