Spatial CRISPR genomics identifies regulators of the tumor microenvironment.
IF: 66.850
Cited by: 54


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 TGFβ and TGFβ-mediated fibroblast activation, indicating that TGFβ-receptor loss on cancer cells increased TGFβ 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 TGFβ responsiveness of cancer cells can affect the TME.


Spatial Transcriptomics
Spatial Genomics
CRISPR screens
TGF beta
cancer immunology
interferon gamma
lung cancer
spatial genomics
spatial transcriptomics
tumor clonality
tumor microenvironment

MeSH terms

Clustered Regularly Interspaced Short Palindromic Repeats
Transforming Growth Factor beta
Tumor Microenvironment


Dhainaut, Maxime
Rose, Samuel A
Akturk, Guray
Wroblewska, Aleksandra
Nielsen, Sebastian R
Park, Eun Sook
Buckup, Mark
Roudko, Vladimir
Pia, Luisanna
Sweeney, Robert
Le Berichel, Jessica
Wilk, C Matthias
Bektesevic, Anela
Lee, Brian H
Bhardwaj, Nina
Rahman, Adeeb H
Baccarini, Alessia
Gnjatic, Sacha
Pe'er, Dana
Merad, Miriam
Brown, Brian D

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