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

Mechanisms by which chemokine CXCL12 functions in hematopoiesis and lymphopoiesis

趋化因子CXCL12在造血和淋巴细胞生成中的作用机制

基本信息

批准号：
15390160
负责人：
NAGASAWA Takashi
金额：
$ 9.79万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390160/
关键词：
chemokine chemokine receptor bone marrow homing hematopoiesis stem cell lymphocyte generative cell

项目摘要

CXC chemokine ligand (CXCL)12 (stromal cell-derived factor (SDF-1)/pre-B-cell-growth-stimulating factor(PBSF)) and its primary physiologic receptor CXCR4 are essential for B cell development and colonization of bone marrow by hematopoietic cells during. In this study, we have analyzed further the roles of CXCL12 in mobilization of hematopoietic cells between and within hematopoietic organs. (1)Hematopoietic stem cells(HSCs) are mobile and sequence of hematopoietic colonization events occurs during ontogeny. We have shown that CXCL12 plays a critical role in homing of HSCs and myeloid cells to bone marrow from the peripheral circulation using a long-term repopulation assay and cell homing assay. (2)B lymphocytes are generated from HSCs and develop within bone marrow and dependency on CXCL12 appears at the earliest stages, pre-pro-B cells. We have found that CXCL12-expressing cells are a small population of stromal cells, had several processes, are scattered throughout bone marrow and located some distance from the cells expressing interleukin (IL)-7. Multipotent hematopoietic progenitors are attached to the processes of CXCL12-expressing cells and pre-pro-B cells adjoin their cell bodies. Maturer pro-B cells, which require IL-7, have moved away and adjoin the IL-7-expressing cells. Maturer pre-B cells are not in contact with IL-7-expressing cells. Furthermore, the end-stage B cells, plasma cells again seed CXCL12-expressing cells. Thus, we have identified stage-specific niches for B lymphopoiesis, demonstrated the B lymphocyte characteristic location and movement between specific niches within bone marrow during development and suggested that CXCL12 maintains the precursors in the niche. Together, CXCL12 is likely to play a critical role in the interaction of hematopoictic cells with the specific cellular niches in bone marrow.

CXC趋化因子配体（CXCL）12（基质细胞衍生因子（SDF-1）/前B细胞生长刺激因子（PBSF））及其主要生理受体CXCR 4是造血干细胞在B细胞发育和骨髓定植过程中所必需的。在这项研究中，我们进一步分析了CXCL 12在造血器官之间和造血器官内造血细胞动员中的作用。（1）造血干细胞（HSCs）是移动的，在个体发育过程中发生一系列造血定植事件。我们已经使用长期再增殖测定和细胞归巢测定表明，CXCL 12在造血干细胞和骨髓细胞从外周循环归巢至骨髓中起关键作用。(2)B淋巴细胞由HSC产生并在骨髓内发育，对CXCL 12的依赖性出现在最早期，即前原B细胞。我们发现CXCL 12表达细胞是一小群基质细胞，有几个突起，分散在整个骨髓中，与表达白细胞介素（IL）-7的细胞有一定距离。多能造血祖细胞附着于表达CXCL 12的细胞的突起，前原B细胞邻接它们的细胞体。需要IL-7的成熟前B细胞已经离开并邻接表达IL-7的细胞。成熟的前B细胞不与表达IL-7的细胞接触。此外，终末期B细胞、浆细胞再次接种表达CXCL 12的细胞。因此，我们已经确定了B淋巴细胞生成的阶段特异性小生境，证明了B淋巴细胞在发育过程中在骨髓内特定小生境之间的特征性位置和运动，并表明CXCL 12维持小生境中的前体。总之，CXCL 12可能在造血细胞与骨髓中特定细胞龛的相互作用中发挥关键作用。