Comprehensive Metabolite Profiling in Single-Cell Systems via Dual-Modal MALDI-Mass Spectrometry Imaging

IF 6.7 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Jie Yuan, Xiafei Li, Xinxin Shen, Pei Xiong, Nanlin Zhu, Yang Ye and Jia Liu*, 
{"title":"Comprehensive Metabolite Profiling in Single-Cell Systems via Dual-Modal MALDI-Mass Spectrometry Imaging","authors":"Jie Yuan,&nbsp;Xiafei Li,&nbsp;Xinxin Shen,&nbsp;Pei Xiong,&nbsp;Nanlin Zhu,&nbsp;Yang Ye and Jia Liu*,&nbsp;","doi":"10.1021/acs.analchem.4c0548010.1021/acs.analchem.4c05480","DOIUrl":null,"url":null,"abstract":"<p >The development of spatial multiomics technologies, particularly matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), has revolutionized our ability to map metabolic processes at single-cell resolution. However, the current techniques face challenges in minimizing matrix interferences and achieving comprehensive metabolite detection across multiple ionization modes. In this study, we present a novel dual-modal MSI workflow that leverages the pairing of 1,5-diaminonaphthalene (DAN) and its hydrochloric salt (DAN-HCl) matrices for sequential detection in positive- and negative-ion modes, respectively. This approach significantly enhanced metabolite coverage, spanning both lipid-based and nonlipid small molecules, while eliminating the need for solvent cleaning steps. Applied to a coculture of cholangiocarcinoma (CCLP1) and hepatic stellate (LX2) cells, the workflow revealed significant metabolic distinctions, including differential accumulation of glycerolipids and energy-related metabolites, highlighting the unique metabolic profiles of each cell type. Additionally, several unidentified metabolites were detected, indicating the potential to discover novel metabolic variations. These findings establish our method as a robust tool for single-cell spatial metabolomics with broad applicability in studying complex cellular interactions and advancing both research and clinical applications.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"97 16","pages":"8729–8737 8729–8737"},"PeriodicalIF":6.7000,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.analchem.4c05480","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0

Abstract

The development of spatial multiomics technologies, particularly matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), has revolutionized our ability to map metabolic processes at single-cell resolution. However, the current techniques face challenges in minimizing matrix interferences and achieving comprehensive metabolite detection across multiple ionization modes. In this study, we present a novel dual-modal MSI workflow that leverages the pairing of 1,5-diaminonaphthalene (DAN) and its hydrochloric salt (DAN-HCl) matrices for sequential detection in positive- and negative-ion modes, respectively. This approach significantly enhanced metabolite coverage, spanning both lipid-based and nonlipid small molecules, while eliminating the need for solvent cleaning steps. Applied to a coculture of cholangiocarcinoma (CCLP1) and hepatic stellate (LX2) cells, the workflow revealed significant metabolic distinctions, including differential accumulation of glycerolipids and energy-related metabolites, highlighting the unique metabolic profiles of each cell type. Additionally, several unidentified metabolites were detected, indicating the potential to discover novel metabolic variations. These findings establish our method as a robust tool for single-cell spatial metabolomics with broad applicability in studying complex cellular interactions and advancing both research and clinical applications.

Abstract Image

通过双模态maldi -质谱成像在单细胞系统中进行综合代谢物分析
空间多组学技术的发展,特别是基质辅助激光解吸/电离质谱成像(MALDI-MSI),已经彻底改变了我们在单细胞分辨率下绘制代谢过程的能力。然而,目前的技术在最小化基质干扰和实现跨多种电离模式的全面代谢物检测方面面临挑战。在这项研究中,我们提出了一种新的双模态MSI工作流程,利用1,5-二氨基萘(DAN)和它的盐酸盐(DAN- hcl)矩阵的配对,分别在正离子和负离子模式下进行顺序检测。这种方法显著增强了代谢物的覆盖范围,涵盖了基于脂质和非脂质的小分子,同时消除了溶剂清洗步骤的需要。应用于胆管癌细胞(CCLP1)和肝星状细胞(LX2)的共培养,该工作流程揭示了显著的代谢差异,包括甘油脂和能量相关代谢物的不同积累,突出了每种细胞类型的独特代谢谱。此外,还检测到几种未识别的代谢物,这表明有可能发现新的代谢变异。这些发现使我们的方法成为单细胞空间代谢组学的强大工具,在研究复杂的细胞相互作用和推进研究和临床应用方面具有广泛的适用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Analytical Chemistry
Analytical Chemistry 化学-分析化学
CiteScore
12.10
自引率
12.20%
发文量
1949
审稿时长
1.4 months
期刊介绍: Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信