Cellular-scale proximity labeling for recording cell spatial organization in mouse tissues.

Area of Science:

• Cell biology
• Chemical biology
• Genomics

Background:

• Proximity labeling is crucial for studying cell-cell interactions.
• Current methods have limited labeling radii, hindering analysis of indirect communication and tissue spatial organization.

Purpose of the Study:

• To develop a novel chemical strategy, QMID, for cell spatial organization analysis with an extended labeling radius.
• To overcome limitations of existing proximity labeling techniques for studying indirect cell communication and tissue architecture.

Main Methods:

• Developed QMID, a chemical strategy utilizing quinone methide (QM) electrophiles produced by surface-installed enzymes.
• QMID enables labeling of proximal cells independent of direct cell-cell contact, with a labeling radius matching cell dimensions.
• Applied QMID in cell coculture and in vivo mouse spleen models, followed by single-cell RNA sequencing.

Main Results:

• QMID successfully revealed gene expression changes in macrophages spatially proximal to tumor cells in coculture.
• Enabled isolation and analysis of proximal CD4+ and CD8+ T cells in mouse spleen.
• Uncovered distinct cell populations and gene expression patterns within immune niches of specific T cell subtypes.

Conclusions:

• QMID offers a powerful tool for dissecting cell spatial organization in complex biological systems.
• The extended labeling radius of QMID facilitates the study of indirect cell communications and tissue microenvironments.
• QMID provides novel insights into immune cell interactions and organization within specific niches.