TY - JOUR
T1 - Thrombopoietin/MPL Signaling Regulates Hematopoietic Stem Cell Quiescence and Interaction with the Osteoblastic Niche
AU - Yoshihara, Hiroki
AU - Arai, Fumio
AU - Hosokawa, Kentaro
AU - Hagiwara, Tetsuya
AU - Takubo, Keiyo
AU - Nakamura, Yuka
AU - Gomei, Yumiko
AU - Iwasaki, Hiroko
AU - Matsuoka, Sahoko
AU - Miyamoto, Kana
AU - Miyazaki, Hiroshi
AU - Takahashi, Takao
AU - Suda, Toshio
N1 - Funding Information:
This work was supported by Grant-in-Aid for Specially Promoted Research and Grant-in-Aid for Young Scientists (A) from The Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan; and by “High-Tech Research Center” Project for Private Universities, matching fund subsidy from MEXT, by a Takeda Science Foundation, and by The Sumitomo Foundation. We acknowledge Ms. Ayako Kumakubo for preparation of tissue sections of BM. We also thank Ms. Ayami Ono for technical assistance.
PY - 2007/12/13
Y1 - 2007/12/13
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stem.2007.10.020
DO - 10.1016/j.stem.2007.10.020
M3 - Article
C2 - 18371409
AN - SCOPUS:36748999351
SN - 1934-5909
VL - 1
SP - 685
EP - 697
JO - Cell stem cell
JF - Cell stem cell
IS - 6
ER -