Spatial CRISPR genomics identifies regulators of the tumor microenvironment.

🤖 Plain-English Summary

While CRISPR screens are helping uncover genes regulating many cell-intrinsic processes, existing approaches are suboptimal for identifying extracellular gene functions, particularly in the tissue context. We found that in Tgfbr2 knockout tumors, the tumor microenvironment (TME) was converted to a fibro-mucinous state, and T cells excluded, concomitant with upregulated TGFβ and TGFβ-mediated fibroblast activation, indicating that TGFβ-receptor loss on cancer cells increased TGFβ bioavailability...

🔑 Key Findings

• Here, we developed an approach for spatial functional genomics called Perturb-map.
• We applied Perturb-map to knock out dozens of genes in parallel in a mouse model of lung cancer and simultaneously assessed how each knockout influenced tumor growth, histopathology, and immune composition.
• Moreover, we paired Perturb-map and spatial transcriptomics for unbiased analysis of CRISPR-edited tumors.

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