Takeda Hiromi, Fujimori Yoshihiro, Kai Shunro, Ogawa Hiroyasu, Nakano Takashi
Laboratory of Cell Transplantation, Institute for Advanced Medical Sciences.
Exp Ther Med. 2010 May;1(3):497-501. doi: 10.3892/etm_00000078. Epub 2010 May 1.
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.
含CUB结构域蛋白1(CDCP1)/CD318是一种单次跨膜分子,在结直肠癌和白血病中高表达。研究还表明它在造血祖细胞中表达。在本研究中,我们分析了CD318在脐血造血干细胞和祖细胞上的表达。脐血单个核细胞去除成熟血细胞谱系(Lin)阳性细胞,然后根据CD34和CD318的表达通过流式细胞术对Lin阴性细胞进行分选。通过集落形成试验分析分选细胞表明,与CD34(+)CD318(-)细胞相比,CD34(+)CD318(+)细胞产生更多的混合集落形成单位和红系爆式集落形成单位衍生集落。CD34(-)CD318(+)和CD34(-)CD318(-)细胞也能产生这些集落,但数量通常较少。当分选细胞在人间充质干细胞单层上培养时,CD34(+)CD318(+)细胞比CD34(+)CD318(-)细胞增殖更旺盛,而CD34(-)CD318(+)和CD34(-)CD318(-)细胞未能增殖。将CD34(+)CD318(+)细胞移植到非肥胖糖尿病/严重联合免疫缺陷病(NOD/SCID)小鼠中可有效重建人细胞,表明CD34(+)CD318(+)细胞具有强大的重症联合免疫缺陷病重建细胞活性。这些发现提示CD34和CD318的共表达可识别造血干细胞的未成熟特性。