Spatial Metabolomics with Specific Protein Profiling for Tissue Biology

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Summary

In their research, scientists developed a novel framework called scSpaMet to simultaneously analyze proteins and metabolites at a single-cell level in male human tissues, focusing on immune and cancer cells. This approach combined untargeted spatial metabolomics with targeted protein imaging, enabling detailed profiling of various cell types and their metabolic landscapes in lung cancer, tonsil, and endometrium tissues, encompassing tens of thousands of individual cells. The study uncovered unique metabolic profiles and competitions among neighboring cells, as well as distinct metabolic states and developmental trajectories within cell types. The scSpaMet's capacity for precise metabolic-protein mapping at the cellular level marks a significant advancement in understanding tissue biology systemically.

Research Criteria

Researchers create a unique method for simultaneous protein and metabolite analysis in individual cells within human tissues. This technique merges specific protein imaging with comprehensive spatial metabolomics. It highlights the critical role of distinguishing cellular identities and metabolic functions, especially in understanding immunity and cancer.

Sample Type

The samples used for the single-cell experiments in this study are human tissues, specifically focusing on immune cells and cancer cells within these tissues. The research includes the analysis of lung tumors and tonsil tissues.

Result—Integrated Metabolite and Protein Profiling at Single Cell Resolution Using the scSpaMet Pipeline

The scSpaMet method marks a breakthrough in immunometabolic research by merging proteomic and metabolic insights at a singular cell level. This technique employs metal-tagged antibodies for tissue staining and employs ToF-SIMS and IMC for metabolic and proteomic analysis, respectively. Its standout capability lies in its high-resolution matching of cellular types with their metabolic states. The method's sophistication is evident in features like pixel-based clustering and enhanced cell registration, instrumental in dissecting lung and tonsil tissue compositions. It further integrates multi-omics approaches and trajectory analysis, deepening the understanding of cellular metabolism and spatial interplays. Leveraging the Leiden algorithm for unguided single-cell proteomic clustering, it unveils complex interactions between cell types and metabolic channels, offering novel perspectives on cellular competition within metabolic contexts.

Fig.1 SpaMet pipeline for high-resolution integrated metabolite and protein profiling¹.

Result—Metabolic States Specific to Cell Types in Lung Cancer Tissues

The study reveals that cancer cells in lung tumors alter their metabolic processes, particularly glycolysis, to support rapid growth, leading to an environment that suppresses immune responses. By using an antibody panel to identify different cell types, including immune and cancer cells, the researchers were able to map the distribution of various metabolites, such as lactate and cholesterol fragments, across these regions. This detailed mapping showed that tumor regions have higher levels of certain metabolites linked to glucose metabolism, while stromal regions exhibit higher cholesterol levels. These findings underscore the complex metabolic interactions within tumors and open up possibilities for targeted therapies that disrupt these metabolic pathways to enhance cancer treatment.

Fig.2 In human lung cancer tissues, scSpaMet detects variations in metabolites between the stromal and tumor regions¹.

Creative Biolabs' Service

Spatial Metabolomics Service

At Creative Biolabs, we've revolutionized our spatial metabolomics capabilities with the introduction of our novel AFAI-MSI technology. This advanced method, a fusion of DESI-MSI with innovative air flow and voltage techniques, facilitates enhanced desolvation, enrichment, and ionization of charged droplets. Our breakthrough dramatically boosts sensitivity and enables us to analyze larger samples over greater distances, significantly broadening our analytical scope beyond just single tissue samples.

Learn more

At Creative Biolabs, we've revolutionized our spatial metabolomics approach by innovatively merging desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with our groundbreaking air flow-assisted ionization technology (AFAI-MSI). This advanced technique leverages airflow and specialized transmission tubes to propel charged droplets, which undergo intensified desolvation, enrichment, and ionization due to the high-speed air currents and voltage applied. Our efforts have dramatically heightened the sensitivity of our detection methods. Additionally, this technological leap allows for a broader range of sample versatility and operational flexibility, making it possible to analyze and visualize larger samples across extended distances, moving beyond the constraints of analyzing only single tissue samples.

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Reference

1. Hu, Thomas, et al. "Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology." Nature Communications 14.1 (2023): 8260.