Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches
Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches
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DOI：
10.1016/j.immuni.2006.10.016
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发表时间：
2006-12-01
期刊：
影响因子：
32.4
通讯作者：
Nagasawa, Takashi
中科院分区：
文献类型：
--
作者：
Sugiyama, Tatsuki;Kohara, Hiroshi;Nagasawa, Takashi
在骨髓中，特殊的微环境龛培育了大量造血干细胞（hsc）。许多造血干细胞位于脉管系统附近，但造血干细胞维持的分子调控机制尚不清楚。在这里，我们发现在成年小鼠中，CXCR4 （CXC趋化因子配体（CXCL） 12的受体）的诱导缺失导致HSC数量的严重减少和对髓毒性损伤的敏感性增加，尽管它不影响更成熟的祖细胞的扩增。大多数造血干细胞与表达大量CXCL12的细胞接触，我们称之为富含CXCL12的网状细胞（CAR）。CAR细胞围绕在窦状内皮细胞周围或位于内皮附近。CXCL12-CXCR4信号在维持静止的HSC池中起着至关重要的作用，CAR细胞似乎是成人骨髓中HSC壁龛（包括血管和内皮壁龛）的关键组成部分。
In the bone marrow, the special microenvironment niches nurture a pool of hematopoietic stem cells (HSCs). Many HSCs reside near the vasculature, but the molecular regulatory mechanism of niches for HSC maintenance remains unclear. Here we showed that the induced deletion of CXCR4, a receptor for CXC chemokine ligand (CXCL) 12 in adult mice, resulted in severe reduction of HSC numbers and increased sensitivity to myelotoxic injury, although it did not impair expansion of the more mature progenitors. Most HSCs were found in contact with the cells expressing high amounts of CXCL12, which we have called CXCL12-abundant reticular (CAR) cells. CAR cells surrounded sinusoidal endothelial cells or were located near the endosteum. CXCL12-CXCR4 signaling plays an essential role in maintaining the quiescent HSC pool, and CAR cells appear to be a key component of HSC niches, including both vascular and endosteal niches in adult bone marrow.