Key Findings and Results 

The study’s results are profound, demonstrating the effectiveness of spatial CITE-seq in multiple tissue types from both mice and humans.

Mouse Tissue Analysis

The method was first applied to various mouse tissues, including the spleen, colon, intestine, and kidney. The researchers successfully mapped 189 proteins and the whole transcriptome, revealing distinct clusters that corresponded well with known anatomical features of these tissues. For instance, in the spleen, five major clusters were identified, corresponding to red and white pulps, microvascular tissue, and other distinct regions. The high sensitivity of the method was highlighted by the detection of nearly 190 proteins per pixel, with an average of 118 proteins detected per pixel in the spleen sample.

Human Tonsil and Skin Analysis

The technique was further validated on human tissues, including the tonsil and a skin biopsy from a COVID-19 mRNA vaccine injection site. In the tonsil, 273 proteins were mapped alongside the transcriptome, revealing spatially distinct germinal center reactions and T cell zones. The skin biopsy analysis uncovered localized peripheral T cell activation at the vaccine injection site, which may be critical in understanding immune responses to vaccination.

Comparison and Validation

The researchers compared spatial CITE-seq results with single-cell CITE-seq (scCITE-seq) and multiplex immunofluorescence imaging. The strong correlation between these datasets validated the accuracy of spatial CITE-seq. The study also demonstrated the integration of spatial CITE-seq data with scRNA-seq data, providing a comprehensive view of cell type distribution and function within tissues.

Implications and Future Directions 

The introduction of spatial CITE-seq opens new avenues in the study of tissue biology, offering a tool with significant potential in fields such as cancer research, immunology, and infectious diseases. The ability to map hundreds of proteins alongside the transcriptome at cellular resolution provides a more detailed understanding of cellular microenvironments and interactions. The researchers also suggested that the technique could be further expanded to map even more proteins, potentially exceeding 1,000, by optimizing sequencing conditions and expanding the range of detectable proteins to include intracellular and extracellular matrix proteins.

Conclusion

Spatial CITE-seq represents a substantial advancement in spatial multi-omics, providing a powerful tool for high-resolution mapping of proteins and the transcriptome within tissues. This method has the potential to transform the understanding of complex tissue biology and disease mechanisms. The study by Liu et al. has set a new standard for spatial omics technologies, offering a glimpse into the future of comprehensive tissue mapping.

Acknowledgment

This research was led by a team of scientists from Yale University, including Yang Liu, Marcello DiStasio, and Rong Fan, among others.The study is fully available in Nature Biotechnology (2023), DOI : 10.1038/s41587-023-01676-0.