Uncovering spatially resolved functional genomics with CRISPR screen sequencing
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. 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 ge
Content
# Uncovering spatially resolved functional genomics with CRISPR screen sequencing
*Published: 2026 May 26*
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. 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.
We also demonstrated the model of the transcription factor-chemokine receptor
axis coupling cell states with chemotaxis. SPAC-seq and TARDIS provide an
effective framework to study spatially resolved functional genomics and pathways
across diverse biological and disease contexts.
DOI: 10.1016/j.cell.2026.04.049