Expression of immunoglobulin superfamily cell adhesion molecules on murine embryonic stem cells
Expression of immunoglobulin superfamily cell adhesion molecules on murine embryonic stem cells
复制标题
DOI：
10.1095/biolreprod57.3.561
复制
发表时间：
1997-09-01
影响因子：
3.6
通讯作者：
King, NJC
中科院分区：
文献类型：
--
作者：
Tian, L;Catt, JW;King, NJC
本研究观察了体外培养的胚胎干细胞（ES细胞）中细胞粘附分子IG超家族（Ig-CAM）的表达。当在白血病抑制因子（LIF）存在下或与成纤维细胞饲养细胞一起培养时，ES细胞保持未分化的表型; > 90%的细胞对标记未分化ES细胞的抗体（ECMA-7）呈阳性反应。使用流式细胞术，在未分化的ES细胞上检测到高浓度的ICAM-1、VCAM-1和NCAM抗原，但未检测到其特异性受体Mac-1、LFA-1和VLA-4。也没有I类或II类主要组织相容性复合体（MHC）抗原表达。表达的ICAM-1是功能性的，因为抗ICAM-1显著（p < 0.0001）阻断ES细胞-淋巴细胞结合。未分化ES细胞上Ig-CAM和MHC-1的表达没有通过用干扰素-γ（IFN-γ）、肿瘤坏死因子α或黄病毒感染（在其他胚胎细胞类型中上调这些分子的试剂）处理细胞而上调。LIF停药后12 h，ICAM-1和NCAM表达明显下降，VCAM-1表达下降。然而，形态学和ECMA-7表达保持不变。在维持在成纤维细胞饲养细胞上的ES细胞上观察到类似的表达模式。这表明LIF或其他细胞因子可以维持未分化细胞上Ig-CAM的表达。用二甲基亚砜处理14天诱导分化。细胞从集落形成变为单层形态，并且类似于60%的细胞群不再表达ECMA-7。在这些细胞中，VCAM-1检测不到，ICAM-1和NCAM已降至低水平。在这些分化的细胞中，ICAM-1和MHC-1可被IFN-γ诱导。这项研究表明，在ES细胞中的Ig-CAM的表达模式可能有一个作用，在定义分化和未分化细胞的表型。
The expression of cell adhesion molecules of the Ig superfamily (Ig-CAM) were examined on embryonic stem (ES) cells during culture in vitro. ES cells maintained an undifferentiated phenotype when cultured in the presence of leukemia inhibitory factor (LIF) or with fibroblast feeder cells; > 90% of cells reacted positively to an antibody (ECMA-7) that marks undifferentiated ES cells. Using flow cytometry, high concentrations of ICAM-1, VCAM-1, and NCAM antigens were detected on undifferentiated ES cells, but their specific receptors, Mac-1, LFA-1, and VLA-4, were not detected. There was also no class I or II major histocompatibility complex (MHC) antigen expression. The ICAM-1 expressed was functional, since anti-ICAM-1 significantly (p < 0.0001) blocked ES cell-lymphocyte binding. Ig-CAM and MHC-1 expression on undifferentiated ES cells was not up-regulated by treatment of cells with interferon-gamma (IFN-gamma), tumor necrosis factor alpha, or flavivirus infection, agents that up-regulate these molecules in other embryonic cell types. Twelve hours after LIF withdrawal, ICAM-1 and NCAM expression decreased significantly, while VCAM-1 was undetectable. However, morphology and ECMA-7 expression remained unchanged. Similar patterns of expression were seen on ES cells maintained on fibroblast feeder cells. This suggests that LIF or other cytokines may maintain the expression of Ig-CAMs on undifferentiated cells. Differentiation was induced by dimethyl sulfoxide treatment for 14 days. Cells changed from a colony-forming to a monolayer morphology, and similar to 60% of the cell population no longer expressed ECMA-7. In these cells, VCAM-1 was undetectable and ICAM-1 and NCAM had declined to low levels. In these differentiated cells, ICAM-1 and MHC-1 were inducible by IFN-gamma. This study suggests that the pattern of expression of the Ig-CAMs in ES cells may have a role in defining the phenotype of differentiated and undifferentiated cells.