Healy L, May G, Gale K, Grosveld F, Greaves M, Enver T
Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12240-4. doi: 10.1073/pnas.92.26.12240.
Although the CD34 antigen is widely used in the identification and purification of hemopoietic stem and progenitor cells, its function within hemopoiesis is unknown. We have investigated this issue by ectopically expressing human (hu) CD34 on the surface of murine hemopoietic cells. Forced expression of hu-CD34 in the thymocytes of transgenic mice did not appear to affect the development, maturation, or distribution of murine T cells but did significantly increase their ability to adhere to bone marrow stromal layers of human but not mouse origin. Ectopic expression of hu-CD34 on murine 416B cells, a multipotential progenitor that expresses murine CD34, yielded similar results. In both cases hu-CD34-dependent adhesion was enhanced by molecular engagement of the hu-CD34 protein using anti-CD34 antibodies. These results provide evidence that CD34 promotes the adhesive interactions of hemopoietic cells with the stromal microenvironment of the bone marrow thereby implicating CD34 in regulation and compartmentalization of stem cells. We propose that CD34 regulates these processes in part via an indirect mechanism, signaling changes in cellular adhesion in response to molecular recognition of an as yet unidentified stromal CD34 counterreceptor or ligand.
尽管CD34抗原广泛用于造血干细胞和祖细胞的鉴定与纯化，但其在造血过程中的功能尚不清楚。我们通过在鼠造血细胞表面异位表达人（hu）CD34来研究这个问题。在转基因小鼠的胸腺细胞中强制表达hu-CD34似乎不影响鼠T细胞的发育、成熟或分布，但确实显著增强了它们与人源而非鼠源骨髓基质层的黏附能力。在表达鼠CD34的多能祖细胞鼠416B细胞上异位表达hu-CD34也得到了类似结果。在这两种情况下，使用抗CD34抗体通过hu-CD34蛋白的分子结合增强了依赖hu-CD34的黏附。这些结果证明CD34促进造血细胞与骨髓基质微环境的黏附相互作用，从而表明CD34参与干细胞的调节和分隔。我们提出CD34部分通过间接机制调节这些过程，即响应尚未鉴定的基质CD34反受体或配体的分子识别，发出细胞黏附变化的信号。
