Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes

Area of Science:

• Biomedical research
• Molecular biology
• Genomics

Background:

• Existing spatial omics technologies are expensive and time-consuming.
• High-dimensional, spatially resolved tissue analysis is crucial for research and diagnostics.

Purpose of the Study:

• To introduce Fluorescence In Situ Hybridization of Cellular HeterogeneIty and gene expression Programs (FISHnCHIPs) for sensitive in situ cell type and gene expression profiling.
• To overcome limitations of current spatial omics technologies.

Main Methods:

• FISHnCHIPs simultaneously images ~2-35 co-expressed genes clustered into modules.
• It achieves high sensitivity and spatial resolution comparable to single-gene FISH.
• The method allows for high-speed, large field-of-view tissue profiling.

Main Results:

• FISHnCHIPs demonstrated ~2-20-fold higher sensitivity than conventional FISH.
• Up to 53 modules were imaged in mouse kidney and brain tissues.
• Spatially restricted cancer-associated fibroblasts were identified in colorectal cancer biopsies.

Conclusions:

• FISHnCHIPs provides a fast, robust, and scalable solution for cell typing in tissues.
• This technology advances the study of tissues in normal physiology and disease pathogenesis.
• FISHnCHIPs has significant implications for biomedical research and diagnostics.