title: Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche.
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 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.
authors: Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University, 35 Shinano-machi, Tokyo, 160-8582, Japan.
authors: Hiroki
authors: H
authors: Yoshihara
authors: Fumio
authors: F
authors: Arai
authors: Kentaro
authors: K
authors: Hosokawa
authors: Tetsuya
authors: T
authors: Hagiwara
authors: Keiyo
authors: K
authors: Takubo
authors: Yuka
authors: Y
authors: Nakamura
authors: Yumiko
authors: Y
authors: Gomei
authors: Hiroko
authors: H
authors: Iwasaki
authors: Sahoko
authors: S
authors: Matsuoka
authors: Kana
authors: K
authors: Miyamoto
authors: Hiroshi
authors: H
authors: Miyazaki
authors: Takao
authors: T
authors: Takahashi
authors: Toshio
authors: T
authors: Suda
mesh_terms: D000818:Animals; D002460:Cell Line; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007399:Interphase; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D053628:Receptors, Thrombopoietin / Q000378:metabolism*; D015398:Signal Transduction; D013926:Thrombopoietin / Q000494:pharmacology / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D019012:Integrin beta1; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin