权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of chemokine CXCL12 and CXCL12 abundant reticular cells in formation of microenvironmental niches for hematopoiesis

趋化因子CXCL12和CXCL12丰富的网状细胞在造血微环境生态位形成中的作用

基本信息

批准号：
17082002
负责人：
NAGASAWA Takashi
金额：
$ 116.61万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17082002/
关键词：
ケモカイン骨髄造血幹細胞 Bリンパ球ニッチ

项目摘要

The special microenvironments known as niches, where hematopoietic stem cells (HSCs) and hematopoietic cells reside are thought to supply the requisite factors and play an essential role in their maintenance and regulation. It has been reported previously that HSCs reside near bone surfaces and/or near the vasculature and that a population of osteoblasts and/or endothelial cells might function as niches for HSCs; however, their functions and molecular regulatory mechanism remain unclear. The chemokine CXCL12 and its receptor CXCR4 are essential for colonization of bone marrow by HSCs during ontogeny and development of B cells. In this project, we have shown that the induced deletion of CXCR4 in adult mice results in severe reduction of HSC numbers. In addition, most HSCs were found in contact with the processes of a small population of non-hematopoietic cells expressing high amounts of CXCL12, termed CXCL12-abundant reticular (CAR) cells, some of which surrounded sinusoidal endothelial cells or were located near the endosteum. CAR cells are scattered throughout bone marrow and have long processes. These findings indicate that CXCL12-CXCR4 signaling plays an essential role in maintaining the HSC pool, and suggest that CAR cells are a key component of HSC niches in bone marrow.

造血干细胞（HSC）和造血细胞所处的特殊微环境被认为提供了必要的因子，并在其维持和调节中起着至关重要的作用。以前有报道称，HSC位于骨表面和/或血管系统附近，成骨细胞和/或内皮细胞群体可能作为HSC的壁龛发挥作用;然而，其功能和分子调控机制仍不清楚。趋化因子CXCL 12及其受体CXCR 4在B细胞的个体发生和发育过程中对HSC在骨髓中的定殖至关重要。在这个项目中，我们已经表明，诱导删除CXCR 4在成年小鼠的结果在严重减少HSC的数量。此外，发现大多数HSC与表达大量CXCL 12的一小群非造血细胞的突起接触，称为CXCL 12丰富的网状（CAR）细胞，其中一些包围窦内皮细胞或位于骨内膜附近。CAR细胞分散在整个骨髓中，并且具有长的突起。这些发现表明CXCL 12-CXCR 4信号传导在维持HSC池中起着至关重要的作用，并表明CAR细胞是骨髓中HSC小生境的关键组分。