EVIDENCE THAT HEMATOPOIETIC STEM-CELLS EXPRESS MOUSE C-KIT BUT DO NOT DEPEND ON STEEL FACTOR FOR THEIR GENERATION
EVIDENCE THAT HEMATOPOIETIC STEM-CELLS EXPRESS MOUSE C-KIT BUT DO NOT DEPEND ON STEEL FACTOR FOR THEIR GENERATION
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DOI：
10.1073/pnas.89.4.1502
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发表时间：
1992-02-15
影响因子：
11.1
通讯作者：
WEISSMAN, IL
中科院分区：
文献类型：
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作者：
IKUTA, K;WEISSMAN, IL
小鼠c-kit受体、指定Kit受体和steel因子的相互作用促进造血祖细胞的增殖和分化。建立针对小鼠Kit受体细胞外部分的单克隆抗体。5%到10%的骨髓细胞表达Kit受体，其中一半缺乏谱系标记的表达。Kit受体在70-80%的Thy-1.1(lo) Lin- Sca-1+细胞上表达，这些细胞表达Thy-1.1抗原水平较低，约占成人骨髓和胎儿肝脏的0.05%；先前的研究表明，这些细胞高度富集于多能造血干细胞（hsc），并且是唯一具有这种活性的造血细胞亚群。来自成人骨髓的hy-1lo Lin-Sca-1+细胞的Kit+亚群中含有脾脏集落形成和长期多系重构活性，而Kit-亚群中没有，这表明Kit受体从最早阶段就在造血干细胞上表达-4。多能造血干细胞。利用缺乏编码功能性钢因子基因的Sl/Sl纯合子胚胎，检测了钢因子在造血干细胞发育和自我更新中的作用。在第13-15天，它们的hsc数量是正常幼崽的30-40%。然而，造血干细胞的绝对数量在Sl/Sl小鼠的胎儿发育过程中增加。结果表明，Kit受体-钢因子相互作用可能不是造血启动和（至少）胎儿造血干细胞自我更新所必需的。
The interaction of the mouse c-kit receptor, designated Kit receptor, and steel factor promotes the proliferation and differentiation of hematopoietic progenitor cells. Monoclonal antibodies against the extracellular portion of the mouse Kit receptor were established. Five percent to 10% of total bone marrow cells expressed the Kit receptor, and half of them lack the expression of lineage markers. The Kit receptor was expressed on 70-80% of Thy-1.1(lo) Lin- Sca-1+ cells, which express Thy-1.1 antigen at a low level and constitute almost-equal-to 0.05% of adult bone marrow and fetal liver; by previous studies, these cells have been shown to be highly enriched for multipotent hematopoietic stem cells (HSCs) and are the only hematopoietic cell subset with this activity. Spleen colony formation and long-term multilineage reconstitution activities were contained in the Kit+ but not in the Kit- subpopulations of Thy-1lo Lin-Sca-1+ cells from adult bone marrow, suggesting that the Kit receptor is expressed on HSCs from the earliest stage-4.e., pluripotent HSCs. The role of steel factor in the development and self-renewal of HSCs was tested with Sl/Sl homozygote fetuses, which lack genes to encode functional steel factor. They were shown to have 30-40% of the number of HSCs on days 13-15 when compared with normal littermates. However, the absolute number of HSCs increased during fetal development in the Sl/Sl mice. The results suggest that the Kit receptor-steel factor interaction may not be essential for the initiation of hematopoiesis and the self-renewal of (at least) fetal HSCs.