Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers
Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers
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DOI：
10.1093/glycob/cwn063
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发表时间：
2008-10-01
期刊：
影响因子：
4.3
通讯作者：
Schneck, Jonathan P.
中科院分区：
文献类型：
--
作者：
Tao, Sheng-Ce;Li, Yu;Schneck, Jonathan P.
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有抵抗力，但糖基化在许多关键的细胞过程中是重要的，这就需要对它们进行有效的分析。为了便于糖基化的研究，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的糖链信号。利用凝集素微阵列，我们建立了24个哺乳动物细胞系的细胞结合和层级组织的二元分析。该阵列还用于记录细胞发育和原代小鼠免疫系统细胞分化过程中细胞表面糖基化的变化。为了确定多糖信号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的多糖特征，并能够使用一个模型病原体来预测甘露糖依赖的趋向性。其次，我们在小鼠模型中使用多糖签名来识别肿瘤干细胞样细胞的新的凝集素生物标记物。因此，凝集素微阵列是分析不同细胞过程的有效工具，包括细胞发育和分化、细胞-细胞通讯、病原体-宿主识别和细胞表面生物标记物鉴定。
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.