組織再生への道―最近の進歩　　造血幹細胞の微小環境「ニッチ」

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  • Regulation of hematopoietic stem cell by the bone marrow microenvironment "niche".
  • ゾウケツ カンサイボウ ノ ビショウ カンキョウ ニッチ

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The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of hematopoietic stem cells (HSCs) with their particular microenvironments, known as the stem cell niches, is critical for the regulation of the HSCs. HSCs are keeping the balance of the quiescence and the self-renewal in the stem cell niche, and are maintaining long-term hematopoiesis. We have recently reported that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and anti-apoptotic, and comprise a side-population (SP) of HSCs, which contact closely to osteoblasts. We also found that angiopoietin-1, a ligand for Tie2, was produced by osteoblasts (OBs) in the bone marrow niche. It suggests that Tie2 and Ang-1 are part of a key signaling interaction between HSCs and niche cells. This signaling pathway regulates the feature of HSCs in the BM niche. The interaction of Tie2 with Ang-1 in vitro induced tight adhesion of HSCs to stromal cells and is sufficient to maintain the long-term blood-repopulating (LTR) activity of HSCs in vivo by preventing cell division. In addition, Ang-1 enhanced the ability of HSCs to become quiescent and also induced their adhesion to bone surface in vivo, resulting protection of HSC compartment from stresses, which suppress hematopoiesis. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.

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