Uncovering spatially resolved functional genomics with CRISPR screen sequencing.

🤖 Plain-English Summary

Spatial omics has advanced our understanding of tissue-level biology, yet tools to systematically link gene functional perturbations to spatial phenotypes and signaling pathways remain limited. We also demonstrated the model of the transcription factor-chemokine receptor axis coupling cell states with chemotaxis.

🔑 Key Findings

• To address this, we developed spatial CRISPR screen sequencing (SPAC-seq), a high-throughput spatial CRISPR screen platform, and TARDIS (target prioritization toolkit for perturbation data in spatial omics), a statistical spatial perturbation analysis toolkit.
• Using SPAC-seq and TARDIS, we linked gene perturbations to spatial phenotypes and pathways, uncovering how Icam1 loss in tumor cells promotes metastasis via immune suppression and macrophage polarization.
• In CD8 T cells, we revealed Cd44's role in regulating spatial phenotypes by interacting with Spp1 on macrophages.

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