CD318/CUB-domain-containing protein 1 expression on cord blood hematopoietic progenitors

CD318/CUB-domain-containing protein 1 expression on cord blood hematopoietic progenitors
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DOI:
10.3892/etm_00000078
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发表时间:
2010-05-01
影响因子:
2.7
通讯作者:
Nakano, Takashi
Nakano, Takashi
中科院分区:
医学4区
文献类型:
--
作者:
Takeda, Hiromi;Fujimori, Yoshihiro;Nakano, Takashi

文献摘要

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CUB结构域包含蛋白1(CDCP1/CD318)是一种在结直肠癌和白血病中高表达的跨膜分子。它也被证明在造血祖细胞中表达。在本研究中,我们分析了CD318在脐血造血干/祖细胞上的表达。去除脐血单个核细胞中的成熟血细胞系(LIN)阳性细胞,根据CD34和CD318的表达,用流式细胞仪对LIN阴性细胞进行分选。集落形成实验分析表明,CD34(+)CD318(+)细胞比CD34(+)CD318(-)细胞产生更多的混合集落形成单位和红系形成单位衍生集落。CD34(-)CD318(+)和CD34(-)CD318(-)细胞也能产生这些克隆,但数量一般较少。在人骨髓间充质干细胞单层培养条件下,CD34(+)CD318(+)细胞的增殖能力明显高于CD34(+)CD318(-)细胞,而CD34(-)、CD318(+)和CD34(-)CD318(-)细胞均不能增殖。将CD34(+)CD318(+)细胞移植到非肥胖型糖尿病/严重联合免疫缺陷病(NOD/SCID)小鼠体内,可有效地重建人类细胞,表明CD34(+)CD318(+)细胞具有较强的SCID再扩增细胞活性。这些发现提示,CD34和CD318的共同表达证实了造血干细胞的不成熟特性。
CUB-domain-containing protein 1 (CDCP1)/CD318 is a single transmembrane molecule highly expressed in colorectal cancer and leukemia. It has also been shown to be expressed in hematopoietic progenitor cells. In this study, we analyzed the expression of CD318 on cord blood hematopoietic stem and progenitor cells. Cord blood mononuclear cells were depleted of mature blood cell linage (Lin)-positive cells and then Lin-negative cells were sorted by flow cytometry based on the expression of CD34 and CD318. Analysis of sorted cells by colony-forming assay showed that CD34(+)CD318(+) cells produced more mixed colony forming units and erythroid burst forming unit-derived colonies than CD34(+)CD318(-) cells. These colonies were also produced by CD34(-)CD318(+) and CD34(-)CD318(-) cells, but were generally fewer in number. When sorted cells were cultured on a monolayer of human mesenchymal stem cells, CD34(+)CD318(+) cells proliferated more abundantly than CD34(+)CD318(-) cells, while CD34(-)CD318(+) and CD34(-)CD318(-) cells failed to proliferate. Transplantation of CD34(+)CD318(+) cells into non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice resulted in efficient reconstitution of human cells, indicating that CD34(+)CD318(+) cells possess strong SCID-repopulating cell activity. These findings suggest that the co-expression of CD34 and CD318 identifies the immature character of hematopoietic stem cells.