Spatial proteomics for understanding the tissue microenvironment

Abstract

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.