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人类细胞中糖基化途径的全球图谱。

Global mapping of glycosylation pathways in human-derived cells.

机构信息

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, China.

Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.

出版信息

Dev Cell. 2021 Apr 19;56(8):1195-1209.e7. doi: 10.1016/j.devcel.2021.02.023. Epub 2021 Mar 16.

Abstract

Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena. A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes. Here, we developed a comprehensive glycosylation mapping tool, termed GlycoMaple, to visualize and estimate glycan structures based on gene expression. We informatically selected 950 genes involved in glycosylation and its regulation. Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses. Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures. Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases. Our systematic approach can accelerate glycan analyses and engineering in mammalian cells.

摘要

聚糖是生物大分子的基本类别之一,参与广泛的生物现象。根据组织或细胞类型和环境变化,可合成多种聚糖结构。在此,我们开发了一种全面的糖基化绘图工具,称为 GlycoMaple,用于基于基因表达可视化和估计聚糖结构。我们通过信息学选择了 950 个参与糖基化及其调控的基因。这些基因的表达谱映射到全球糖代谢途径上,以预测聚糖结构,并通过糖组学分析进行验证。基于对 N-聚糖加工的预测,我们构建了 40 个 N-聚糖加工基因敲除 HEK293 细胞系,并分析了基因敲除对聚糖结构的影响。最后,使用公开数据库估计和比较了 64 个细胞系、37 种组织和原发性结肠肿瘤组织的聚糖结构。我们的系统方法可以加速哺乳动物细胞中的聚糖分析和工程。

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