The paper introduce SPAC-seq, a high-throughput technology that combines CRISPR gene editing with spatial transcriptomics to map functional genomics within complex tissue environments. Accompanied by a statistical toolkit called TARDIS, this framework allows researchers to link specific gene perturbations to their physical location and biological impact in vivo. The study utilizes these tools to uncover how the loss of Icam1 facilitates tumor metastasis by creating immunosuppressive niches and how CD44 acts as a critical regulator of T cell infiltration and survival. By disrupting the SPP1-CD44 axis, the authors demonstrate that T cell anti-tumor immunity can be significantly enhanced through reduced oxidative stress. Furthermore, the research identifies a transcriptional-chemotaxis axis where the factor Bhlhe40 governs the spatial positioning of immune cells relative to the tumor microenvironment. Ultimately, these sources present a robust platform for investigating the spatiotemporal dynamics of disease and identifying novel therapeutic targets.

References:

• Zhang H, Zhang Z, Wang P .Uncovering spatially resolved functional genomics with CRISPR screen sequencing. Cell, 2026; 0

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