Abstract
Traditional immunohistochemistry (IHC) is inherently limited by its ability to analyze only several markers within a histological tissue section at a given time, which hinders in-depth characterization and phenotyping of tissues. Imaging mass cytometry (IMC), which combines IHC using metal-labeled antibodies with laser ablation and detection using mass cytometry by time-of-flight, overcomes this limitation with the capability to simultaneously analyze up to 40 protein markers to generate high-dimensional images from a single tissue section. IMC analysis preserves tissue architecture and spatial cellular relationships that would otherwise be lost or significantly altered in applications requiring tissue dissociation, such as flow cytometry or single-cell RNA sequencing. Resulting high-dimensional histological images permit spatially conserved analysis to identify unique cell populations, cellular interactions and avoidances, and insight into activation and behavioral status based on tissue location. IMC can be performed on both frozen and formalin-fixed paraffin-embedded tissue, allowing for previously banked samples to be analyzed and correlated with known clinical outcomes. Expectedly, IMC will change the landscape of investigative pathology, particularly when used in coordination with multiomic platforms to combine transcriptomic and proteomic data at a single-cell resolution. Here, we aim to highlight the potential utility of IMC within dermatologic research and clinical applications.
Highlights
Tissue architecture plays an essential role in both physiological and pathological processes necessary to understand normal homeostasis and the development of disease
We describe the potential applications of Imaging mass cytometry (IMC) for dermatologic research and practice
Recent work has shown how IMC integrates with transcriptomics to enable unparalleled multiomics analysis that has begun to characterize previously unknown cell populations and interactions to shed light on disease pathogenesis
Summary
Tissue architecture plays an essential role in both physiological and pathological processes necessary to understand normal homeostasis and the development of disease. Traditional immunohistochemistry (IHC) or immunofluorescence (IF) can quantify molecular markers to supplement H&E staining, it is inherently limited by its ability to analyze only several markers from a single section at a time, which hinders in-depth characterization and phenotyping of tissues. These limitations preclude IHC from simultaneously phenotyping multiple cell types, cellular interactions, and cellular states in parallel with tissue markers. IMC overcomes the limitations of traditional IHC and IF with the current capacity to analyze up to 40 targets from a single scan with 135 available detection channels, significantly augmenting the ability to evaluate complex cellular systems and processes.
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