基于质谱技术的细胞成像研究  

Mass Spectrometry-based Cell Imaging

作　　者：周鹏[1] 王欣 罗茜[2] 赵超 ZHOU Peng;WANG Xin;LUO Qian;ZHAO Chao(Department of Ultrasound,First Affiliated Hospital of Shenzhen University Health Science Center,Shenzhen Second People’s Hospital,Shenzhen 518035,China;Institute of Scientific Instrumentation,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;College of Pharmacy,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]深圳市第二人民医院(深圳大学第一附属医院)超声科,深圳518035 [2]中国科学院深圳先进技术研究院科学仪器研究所(集群),深圳518055 [3]山西医科大学药学院,太原030001

出　　处：《生物化学与生物物理进展》2025年第4期858-868,共11页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(22176195);广东省人才项目(2021QN02Y028);国家重点研发计划(2022YFF0705003);深圳市基础研究重点项目(JCYJ20210324115811031);深圳市抑郁症精准诊断与治疗重点实验室项目(ZDSYS202206061006 06014);广东省科技创新平台高等级生物安全实验室建设项目(2021B1212030004)资助。

摘　　要：细胞模型可以模拟多种生命状态和疾病发展,包括单细胞、二维(2D)细胞、三维(3D)细胞微球和类器官等模型,是解析错综复杂的生物化学问题的重要工具。近年来,以细胞作为实验模型,采用质谱技术并结合形态学分析,可以从时空水平获得细胞中多种物质分子的量变和空间分布变化,包括代谢物和脂质等内源生物小分子、药物和环境污染物等外源小分子、蛋白质和多肽等內源生物大分子,为考察细胞-细胞相互作用、肿瘤细胞微环境、细胞生物信息时空异质性提供了可能。本文综述了基于质谱技术的细胞成像研究,包括细胞模型的选择和制备、细胞模型的形态学分析、质谱空间组学技术、质谱流式等技术的选择和方法发展及其相关应用。最后,提出了该领域面临的难点问题和未来的发展方向。Cell models can simulate a variety of life states and disease developments,including single cells,two-dimensional(2D)cell cultures,three-dimensional(3D)multicellular spheroids,and organoids.They are essential tools for addressing complex biochemical questions.With continuous advancements in biological and cellular analysis technologies,in vitro cellular models designed to answer scientific questions have evolved rapidly.Early in vitro models primarily relied on 2D systems,which failed to accurately replicate the complex cellular compositions and microenvironmental interactions observed in vivo,let alone support sophisticated investigations into cellular biological functions.Subsequent improvements in cell culture techniques led to the development of 3D culture-based models,such as cellular spheroids.The advent of pluripotent stem cell technology further advanced the development of organoid systems,which closely mimic human organ development.Compared to traditional 2D models,both 3D cellular models and organoids offer significant advantages,including personalization and enhanced physiological relevance,making them particularly suitable for exploring molecular mechanisms of disease progression,discovering novel cellular and biomolecular functions,and conducting related studies.The imaging analysis of common cellular models primarily employs labeling-based methods for in situ imaging of targeted genes,proteins,and small-molecule metabolites,enabling further research on cell types,states,metabolism,and drug efficacy.However,these approaches have drawbacks such as poor labeling specificity and complex experimental procedures.By using cells as experimental models,mass spectrometry technology combined with morphological analysis can reveal quantitative changes and spatial distributions of various biological substances at the spatiotemporal level,including metabolites,proteins,lipids,peptides,drugs,environmental pollutants,and metals.This allows for the investigation of cell-cell interactions,tumor microenvironments,and

关 键 词：细胞成像 空间组学 质谱 时空异质性 

分 类 号：Q7[生物学—分子生物学] O657.6[理学—分析化学]