Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche

被引：588

作者：

Yoshihara, Hiroki ^{[1
,2
]}

Arai, Fumio ^{[1
]}

Hosokawa, Kentaro ^{[1
]}

Hagiwara, Tetsuya

Takubo, Keiyo ^{[1
]}

Nakamura, Yuka ^{[1
]}

Gomei, Yumiko ^{[1
]}

Iwasaki, Hiroko ^{[1
]}

Matsuoka, Sahoko ^{[1
]}

Miyamoto, Kana ^{[1
]}

Miyazaki, Hiroshi ^{[3
]}

Takahashi, Takao ^{[2
]}

Suda, Toshio ^{[1
]}

机构：

[1] Keio Univ, Dept Cell Differentiat, Sakaguchi Lab Dev Biol, Shinjuku Ku, Tokyo 1608582, Japan

[2] Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, Tokyo 1608582, Japan

[3] Kirin Pharma Co Ltd, Discovery Res Labs, Takasaki, Gunma 3701295, Japan

来源：

CELL STEM CELL | 2007年 / 1卷 / 06期

关键词：

D O I：

10.1016/j.stem.2007.10.020

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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/MPIL signaling upregulated beta 1-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.

引用

页码：685 / 697

页数：13

共 49 条

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