School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.
Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen 518055, China and Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, China.
Analyst. 2021 Jun 14;146(12):3777-3798. doi: 10.1039/d1an00472g.
The human body comprises rich populations of cells, which are arranged into tissues and organs with diverse functionalities. These cells exhibit a broad spectrum of phenotypes and are often organized as a heterogeneous but sophisticatedly regulated ecosystem - tissue microenvironment, inside which every cell interacts with and is reciprocally influenced by its surroundings through its life span. Therefore, it is critical to comprehensively explore the cellular machinery and biological processes in the tissue microenvironment, which is best exemplified by the tumor microenvironment (TME). The past decade has seen increasing advances in the field of spatial proteomics, the main purpose of which is to characterize the abundance and spatial distribution of proteins and their post-translational modifications in the microenvironment of diseased tissues. Herein, we outline the achievements and remaining challenges of mass spectrometry-based tissue spatial proteomics. Exciting technology developments along with important biomedical applications of spatial proteomics are highlighted. In detail, we focus on high-quality resources built by scalpel macrodissection-based region-resolved proteomics, method development of sensitive sample preparation for laser microdissection-based spatial proteomics, and antibody recognition-based multiplexed tissue imaging. In the end, critical issues and potential future directions for spatial proteomics are also discussed.
人体包含丰富的细胞群体，这些细胞被排列成具有不同功能的组织和器官。这些细胞表现出广泛的表型，并且通常被组织成一个异质但复杂调节的生态系统——组织微环境，在这个环境中，每个细胞在其生命周期内通过与周围环境相互作用并相互影响。因此，全面探索组织微环境中的细胞机制和生物学过程至关重要，这在肿瘤微环境（TME）中得到了最好的体现。过去十年，空间蛋白质组学领域取得了越来越多的进展，其主要目的是描述疾病组织微环境中蛋白质及其翻译后修饰的丰度和空间分布。在此，我们概述了基于质谱的组织空间蛋白质组学的成就和遗留挑战。强调了空间蛋白质组学令人兴奋的技术发展和重要的生物医学应用。具体来说，我们重点介绍了基于刀片宏观解剖的区域解析蛋白质组学所构建的高质量资源、基于激光微切割的空间蛋白质组学的敏感样品制备方法的发展，以及基于抗体识别的多重组织成像。最后，还讨论了空间蛋白质组学的关键问题和潜在的未来发展方向。
