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通过全糖组学和聚焦蛋白质糖组学分析发现新型聚糖相关生物标志物。

Novel glycan-related biomarker discovery by total glycomic and focused protein glycomic analyses.

作者信息

Hanamatsu Hisatoshi, Suda Goki, Ohara Masatsugu, Kurogochi Masaki, Sakamoto Naoya, Furukawa Jun-Ichi

机构信息

Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Japan.

Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

出版信息

J Hum Genet. 2025 Aug 6. doi: 10.1038/s10038-025-01377-3.

Abstract

The cell surface is covered with a variety of glycan subtypes (sub-glycans) such as N-glycans, O-glycans, glycosphingolipid-glycans, and glycosaminoglycans, which are collectively called the glycocalyx. The expression patterns of sub-glycans change in response to various biological events during disease pathogenesis; however, the structures of all major sub-glycans and their relative concentrations in a cell have been hardly reported. Total glycomic analysis, which comprehensively measures all major sub-glycans, is a powerful tool to discover cellular and clinical biomarkers. In this review, we provide an overview of the analytical methods for sub-glycans and the total glycome in cultured cell lines, human serum, mouse brain tissue, and human osteoarthritis cartilage. This approach not only facilitates characterization of cells, but also has applications for hierarchical clustering analysis, glycan-related biomarker discovery, and investigation of the relationship between sub-glycans and gene expression levels using the total glycome. Moreover, we discuss our recent research focused on identifying potential biomarkers of nonalcoholic fatty liver disease. These glycomic technologies are expected to contribute to diagnostics and drug development for rare diseases in the future.

摘要

细胞表面覆盖着多种聚糖亚型(亚聚糖),如N-聚糖、O-聚糖、糖鞘脂聚糖和糖胺聚糖,它们统称为糖萼。在疾病发病过程中,亚聚糖的表达模式会因各种生物学事件而发生变化;然而,几乎没有关于所有主要亚聚糖的结构及其在细胞中的相对浓度的报道。全面测量所有主要亚聚糖的全糖组分析是发现细胞和临床生物标志物的有力工具。在这篇综述中,我们概述了在培养细胞系、人血清、小鼠脑组织和人骨关节炎软骨中分析亚聚糖和全糖组的方法。这种方法不仅有助于细胞表征,还可应用于层次聚类分析、聚糖相关生物标志物发现以及使用全糖组研究亚聚糖与基因表达水平之间的关系。此外,我们讨论了我们最近专注于识别非酒精性脂肪性肝病潜在生物标志物的研究。这些糖组学技术有望在未来为罕见病的诊断和药物开发做出贡献。

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