Emerging Techniques in Spatial Multiomics: Fundamental Principles and Applications to Dermatology

Area of Science:

• Molecular pathology
• Genomics
• Proteomics
• Epigenomics
• Dermatology

Background:

• Traditional molecular pathology techniques like genomic and proteomic profiling require tissue dissociation, leading to loss of critical histologic and spatial information.
• Existing methods often necessitate labeling multiple tissue slices for comprehensive analysis, increasing complexity and potential for error.

Purpose of the Study:

• To review the principles, advantages, limitations, and potential applications of emerging spatial multi-omic technologies.
• To highlight how these technologies can advance dermatologic research by preserving spatial context in molecular profiling.

Main Methods:

• Spatial multi-omic technologies enable multiplexed visualization of genomic, proteomic, and epigenomic targets within a single tissue slice.
• These technologies offer spatially-resolved single-cell resolution, capable of capturing DNA, genome accessibility, histone modifications, and proteins concurrently.
• Review of current literature and technological advancements in spatial biology.

Main Results:

• Spatial multi-omics overcomes the limitations of tissue dissociation by analyzing multiple molecular layers within intact tissue.
• The technology allows for joint profiling of diverse molecular channels, moving beyond spatial transcriptomics to include DNA, epigenetics, and proteins.
• Enables detailed spatial mapping of molecular features at single-cell resolution.

Conclusions:

• Spatial multi-omics represents a significant advancement for molecular pathology, particularly in dermatology, by retaining spatial context.
• This approach facilitates novel investigations into complex biological questions, such as copy number variations, clonal heterogeneity, and enhancer dysregulation within the skin.
• The technology promises to illuminate the intricate cellular and molecular heterogeneity of skin conditions.