Tao Sheng-Ce, Li Yu, Zhou Jiangbing, Qian Jiang, Schnaar Ronald L, Zhang Ying, Goldstein Irwin J, Zhu Heng, Schneck Jonathan P
Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD 21205, USA.
Glycobiology. 2008 Oct;18(10):761-9. doi: 10.1093/glycob/cwn063. Epub 2008 Jul 14.
Glycosylation is among the most complex posttranslational modifications with an extremely high level of diversity that has made it refractory to high-throughput analyses. Despite its resistance to high-throughput techniques, glycosylation is important in many critical cellular processes that necessitate a productive approach to their analysis. To facilitate studies in glycosylation, we developed a high-throughput lectin microarray for defining mammalian cell surface glycan signatures. Using the lectin microarray we established a binary analysis of cell binding and hierarchical organization of 24 mammalian cell lines. The array was also used to document changes in cell surface glycosylation during cell development and differentiation of primary murine immune system cells. To establish the biological and clinical importance of glycan signatures, the lectin microarray was applied in two systems. First, we analyzed the cell surface glycan signatures and were able to predict mannose-dependent tropism using a model pathogen. Second, we used the glycan signatures to identify novel lectin biomarkers for cancer stem-like cells in a murine model. Thus, lectin microarrays are an effective tool for analyzing diverse cell processes including cell development and differentiation, cell-cell communication, pathogen-host recognition, and cell surface biomarker identification.
糖基化是最复杂的翻译后修饰之一,具有极高的多样性,这使得它难以进行高通量分析。尽管它对高通量技术具有抗性,但糖基化在许多关键的细胞过程中都很重要,因此需要一种有效的分析方法。为了促进糖基化研究,我们开发了一种高通量凝集素微阵列,用于定义哺乳动物细胞表面聚糖特征。利用凝集素微阵列,我们对24种哺乳动物细胞系进行了细胞结合的二元分析和层次组织分析。该阵列还用于记录原代小鼠免疫系统细胞在细胞发育和分化过程中细胞表面糖基化的变化。为了确定聚糖特征的生物学和临床重要性,凝集素微阵列被应用于两个系统。首先,我们分析了细胞表面聚糖特征,并能够使用模型病原体预测甘露糖依赖性嗜性。其次,我们利用聚糖特征在小鼠模型中鉴定癌症干细胞样细胞的新型凝集素生物标志物。因此,凝集素微阵列是分析包括细胞发育和分化、细胞间通讯、病原体-宿主识别和细胞表面生物标志物鉴定在内的各种细胞过程的有效工具。