Universal recording of cell-cell contacts in vivo for interaction-based transcriptomics

Area of Science:

• Immunology
• Cell Biology
• Biotechnology

Background:

• Cellular interactions are critical for tissue organization and immune cell regulation.
• Previous methods like LIPSTIC were limited to specific receptor-ligand pairs (CD40L-CD40).
• A broader approach is needed to study diverse transient cell-cell contacts in vivo.

Purpose of the Study:

• To develop a universal method (uLIPSTIC) for tracking diverse cell-cell interactions in vivo.
• To overcome the limitations of previous receptor-specific interaction labeling techniques.
• To broadly apply the technology to various immunological contexts.

Main Methods:

• Development of a universal LIPSTIC (uLIPSTIC) technique enabling label transfer between interacting cells regardless of specific receptors.
• Application of uLIPSTIC to study T cell priming, regulatory T cell interactions, and T follicular helper cell interactions.
• Integration of uLIPSTIC with single-cell transcriptomics to catalog immune-intestinal epithelial cell interactions.

Main Results:

• uLIPSTIC successfully records interactions among immune cells and between immune and non-immune cells.
• Demonstrated utility in monitoring CD8+ T cell priming by dendritic cells.
• Identified germinal center T follicular helper cells interacting with B cells.
• Cataloged immune cell interactions with intestinal epithelial cells, revealing stepwise adaptation of CD4+ T cells.

Conclusions:

• uLIPSTIC broadly captures diverse immune cell interactions in vivo.
• Demonstrates stepwise interaction acquisition by T cells in intestinal tissue.
• Provides a powerful technology for studying cell-cell communication in various biological systems.