| First Author | Dhainaut M | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 7 | Pages | 1223-1239.e20 |
| PubMed ID | 35290801 | Mgi Jnum | J:328746 |
| Mgi Id | MGI:7259965 | Doi | 10.1016/j.cell.2022.02.015 |
| Citation | Dhainaut M, et al. (2022) Spatial CRISPR genomics identifies regulators of the tumor microenvironment. Cell 185(7):1223-1239.e20 |
| abstractText | 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. 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. 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 TGFbeta and TGFbeta-mediated fibroblast activation, indicating that TGFbeta-receptor loss on cancer cells increased TGFbeta bioavailability and its immunosuppressive effects on the TME. These studies establish Perturb-map for functional genomics within the tissue at single-cell resolution with spatial architecture preserved and provide insight into how TGFbeta responsiveness of cancer cells can affect the TME. |
