瑞典皇家理工学院Simon Fredriksson等研究人员合作开发出新方法，可通过测序对单细胞进行空间蛋白质组学研究。相关论文于2024年5月8日在线发表在《自然—方法学》杂志上。

研究人员表示，细胞表面蛋白质的空间分布制约着免疫系统的重要过程，如细胞间的交流和移动。然而，荧光显微镜在推动亚细胞水平空间蛋白质组学发现所需的多路复用和通量方面的可扩展性有限。

附：英文原文

Title: Molecular pixelation: spatial proteomics of single cells by sequencing

Author: Karlsson, Filip, Kallas, Tomasz, Thiagarajan, Divya, Karlsson, Max, Schweitzer, Maud, Navarro, Jose Fernandez, Leijonancker, Louise, Geny, Sylvain, Pettersson, Erik, Rhomberg-Kauert, Jan, Larsson, Ludvig, van Ooijen, Hanna, Petkov, Stefan, Gonzlez-Granillo, Marcela, Bunz, Jessica, Dahlberg, Johan, Simonetti, Michele, Sathe, Prajakta, Brodin, Petter, Barrio, Alvaro Martinez, Fredriksson, Simon

Issue&Volume: 2024-05-08

Abstract: The spatial distribution of cell surface proteins governs vital processes of the immune system such as intercellular communication and mobility. However, fluorescence microscopy has limited scalability in the multiplexing and throughput needed to drive spatial proteomics discoveries at subcellular level. We present Molecular Pixelation (MPX), an optics-free, DNA sequence-based method for spatial proteomics of single cells using antibody–oligonucleotide conjugates (AOCs) and DNA-based, nanometer-sized molecular pixels. The relative locations of AOCs are inferred by sequentially associating them into local neighborhoods using the sequence-unique DNApixels, forming >1,000 spatially connected zones per cell in 3D. For each single cell, DNA-sequencing reads are computationally arranged into spatial proteomics networks for 76 proteins. By studying immune cell dynamics using spatial statistics on graph representations of the data, we identify known and new patterns of spatial organization of proteins on chemokine-stimulated Tcells, highlighting the potential of MPX in defining cell states by the spatial arrangement of proteins.

DOI: 10.1038/s41592-024-02268-9

Source: https://www.nature.com/articles/s41592-024-02268-9