Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin.
Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin.
复制标题
原始人类多能造血祖细胞分化为单个谱系克隆祖细胞，伴随着与纤连蛋白相互作用的改变。
DOI：
10.1084/jem.174.3.693
复制
发表时间：
1991-09-01
期刊：
影响因子：
--
通讯作者：
McGlave PB
中科院分区：
文献类型：
--
作者：
Verfaillie CM;McCarthy JB;McGlave PB
我们之前已经证明，来自人类骨髓的原始祖细胞，称为长期骨髓培养起始细胞（LTBMC-IC），能强烈地粘附在辐照过的骨髓基质上，而更成熟的克隆祖细胞则不能。在这项研究中，我们研究了这些祖细胞和骨髓基质成分之间的相互作用。(a)我们证明原始LTBMC-IC和更成熟的克隆祖细胞都粘附在完整的纤维连接蛋白上。(b)原始LTBMC-IC和多系CFU-MIX祖细胞粘附在33/66 kD cooh末端肝素结合细胞粘附促进纤维连接蛋白片段上，但其粘附在75 kD RGDS依赖性细胞结合片段上的粘附程度明显较低。相比之下，分化程度更高的单系祖细胞对33/66 kD RGDS独立和75 kD RGDS依赖的纤维连接蛋白细胞粘附片段的粘附程度相同。(c)原始LTBMC-IC和克隆祖细胞都粘附在33/66 kD细胞粘附促进片段FN-C/H I、FN-C/H II和CS1中三个已知的细胞附着位点上。然而，LTBMC-IC和CFU-MIX祖细胞对FN-C/H II的粘附明显优于对FN-C/H I和CS1细胞附着位点的粘附。相比之下，单系祖细胞粘附在33/66 kD细胞粘附促进片段的所有三个细胞附着位点上的效果相同。(d)最后，肽FN-C/H II可以部分抑制原始LTBMC-IC对完整辐照基质的粘附，而FN-C/H II与肽FN-C/H I和CS1的结合几乎可以完全抑制原始LTBMC-IC对完整辐照基质的粘附。本研究表明，原始造血祖细胞和细胞外基质成分纤维连接蛋白之间可以发生粘附相互作用。纤维连接蛋白的33/66 kD细胞粘附促进片段和75 kD rgds依赖性细胞粘附片段粘附的特异性变化与原始多系祖细胞向固定单系祖细胞的分化有关。这种与纤维连接蛋白黏附相互作用的差异可能允许处于不同分化阶段的造血祖细胞与骨髓微环境的特定支持位点相互作用。最后，通过FN-C/H II、FN-C/H I和CS1肽阻断LTBMC-IC对完整辐照基质的粘附能力表明，负责这种相互作用的受体可能在原始祖细胞归巢到骨髓中很重要。
We have previously demonstrated that primitive progenitors from human bone marrow termed long term bone marrow culture initiating cells (LTBMC-IC) adhere avidly to irradiated bone marrow stroma, while more mature clonogenic progenitors fail to do so. In this study we examine the interaction between these progenitors and components of the bone marrow stroma. (a) We demonstrate that both primitive LTBMC-IC and more mature clonogenic progenitors adhere to intact fibronectin. (b) Primitive LTBMC-IC and multi-lineage CFU-MIX progenitors adhere to the 33/66 kD COOH-terminal heparin-binding cell-adhesion promoting fragment of fibronectin, but adhere significantly less to its 75 kD RGDS- dependent cell-binding fragment. In contrast, more differentiated single-lineage progenitors adhere equally well to the 33/66 kD RGDS independent and the 75 kD RGDS-dependent cell-adhesion fragments of fibronectin. (c) Both primitive LTBMC-IC and clonogenic progenitors adhere to the three known cell-attachment sites in the 33/66 kD cell- adhesion promoting fragment, FN-C/H I, FN-C/H II and CS1. However, LTBMC-IC and CFU-MIX progenitors adhere significantly better to FN-C/H II than to the flanking FN-C/H I and CS1 cell-attachment sites. In contrast, single-lineage progenitors adhere equally well to all three cell attachment sites in the 33/66 kD cell-adhesion promoting fragment. (d) Finally, adhesion of primitive LTBMC-IC to intact irradiated stroma can be inhibited partially by peptide FN-C/H II and almost completely by a combination of FN-C/H II and peptide FN-C/H I and CS1. This study demonstrates that adhesive interactions between primitive hematopoietic progenitors and the extracellular matrix component fibronectin can occur. Specific changes in adhesion to the 33/66 kD cell-adhesion promoting fragment and the 75 kD RGDS-dependent cell-adhesion fragment of fibronectin are associated with differentiation of primitive multi- lineage progenitors into committed single-lineage progenitors. Such differences in adhesive interaction with fibronectin may allow hematopoietic progenitors at various stages of differentiation to interact with specific supportive loci of the bone marrow microenvironment. Finally, the ability to block adhesion of LTBMC-IC to intact irradiated stroma with peptides FN-C/H II, FN-C/H I and CS1 suggests that receptors responsible for this interaction may be important in the homing of primitive progenitors to the bone marrow.