Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial...

Area of Science:

• Single-cell genomics
• Spatial transcriptomics
• Cancer biology

Background:

• Characterizing tumor ecosystems requires understanding cellular composition and spatial organization.
• Spatial relationships and functional interactions within tumors remain challenging to define.

Purpose of the Study:

• To create a detailed spatial map of healthy and dysplastic colon cellular ecosystems.
• To investigate the association between cellular organization and colorectal cancer (CRC) progression.
• To develop a framework for extrapolating findings from mouse models to human diseases.

Main Methods:

• Combined single-cell RNA sequencing (scRNA-seq), Slide-seq spatial transcriptomics, and in situ multiplex RNA analysis.
• Profiled inducible genetic CRC mouse models.
• Assigned cell types and expression programs to spatial locations and computationally identified regional features.

Main Results:

• Tumors exhibit distinct cellular neighborhoods with specific cell subtypes, expression programs, and local interactions.
• Cell composition and spatial layout features are conserved between mouse models and human CRC.
• Mouse-derived neighborhood features correlate with malignancy and clinical outcomes in human tumors.

Conclusions:

• The study provides a comprehensive framework for mapping tissue ecosystems and their disease associations.
• Findings highlight the translational relevance of mouse models for understanding human CRC.
• The developed tools facilitate the extrapolation of experimental findings to human diseases.