基于液质联用的单细胞蛋白质组学研究进展

Progress of liquid chromatography and mass spectrometry-based single-cell proteomics

蛋白质是细胞功能的主要执行者,由于其无法在体外进行扩增,单细胞蛋白质组学技术相较单细胞基因组学和转录组学技术而言发展相对滞后。传统的蛋白质组学技术可获得大量细胞蛋白表达的平均值,但忽略了细胞亚型及细胞异质性等信息。单细胞水平的蛋白质分析有助于阐明细胞不同表型与异质性的分子基础。随着质谱仪的快速发展,基于质谱的方法将单细胞蛋白质组学推向新的高度。本文综述了近年来基于液质联用方法的单细胞蛋白质组学在单细胞挑选、样品前处理、同位素标签技术、肽段分离、质谱采集、数据分析等方面的研究进展,及其在生物医学研究中的应用,并对未来单细胞蛋白质组学面临的挑战和发展前景进行了展望。单细胞蛋白质组学技术的进步将为生物医学研究领域提供新的思路和解决方案,并加深我们对人类健康和疾病的理解。

Proteins are the main functional executor of cellular function.Due to the fact that proteins could not be amplified in vitro,the development of single-cell proteomics technology lags behind single-cell genomics and transcriptomics technologies.The traditional proteomics technology detects the average protein expression levels from large amounts of cells;nevertheless,it is unable to address the cell subtypes and heterogeneity among individual cells.Analysis of proteins at the single-cell level can help characterize the molecular basis of cell phenotypes and heterogeneity.With the rapid development of mass spectrometers,mass spectrometry-based methods have pushed single-cell proteomics to a new level.In this review,we summarized the recent research progress of single-cell proteomics methods based on LC-MS/MS,including single cell selection,sample preparation,isotope labelling technology,peptide separation,mass spectrometry analysis and data analysis,and its applications in biomedical research.The challenges and prospects of single-cell proteomics in the future are also prospected.Advances in single cell proteomics will provide new ideas and methods for biomedical research and deepen our understanding of human health and disease.