Spatial epigenome-transcriptome co-profiling of mammalian tissues.

Area of Science:

• Molecular Biology
• Genomics
• Neuroscience

Background:

• Spatial transcriptomics and epigenomics are key tools for cellular state analysis in tissues.
• Current methods analyze only one omics layer, limiting mechanistic understanding across the central dogma.
• Investigating the interplay between epigenetics and gene expression in situ is crucial.

Purpose of the Study:

• To develop and present novel technologies for joint, spatially resolved, genome-wide profiling of epigenomes and transcriptomes.
• To enable simultaneous analysis of chromatin accessibility or histone modifications with gene expression on the same tissue section.
• To explore epigenetic regulation of cellular phenotypes and dynamics within tissue architecture.

Main Methods:

• Developed two technologies for cosequencing chromatin accessibility and gene expression.
• Developed two technologies for cosequencing histone modifications (H3K27me3, H3K27ac, H3K4me3) and gene expression.
• Applied these methods to embryonic/juvenile mouse brain and adult human brain at near-single-cell resolution.

Main Results:

• Achieved spatially resolved, genome-wide joint profiling of epigenome and transcriptome.
• Identified highly concordant tissue features between spatial epigenome and transcriptome data.
• Observed distinct patterns, indicating differential roles of epigenetics and transcription in defining cell states.

Conclusions:

• Linking epigenome and transcriptome pixel-by-pixel reveals new insights into spatial epigenetic priming, differentiation, and gene regulation.
• These technologies offer a powerful approach to study tissue architecture and cell dynamics.
• The developed methods hold significant interest for life science and biomedical research.