美国西奈山伊坎医学院Brian D. Brown研究小组利用空间CRISPR基因组学揭示肿瘤微环境的调节因子。2022年3月14日，《细胞》杂志在线发表了这项成果。
Author: Maxime Dhainaut, Samuel A. Rose, Guray Akturk, Aleksandra Wroblewska, Sebastian R. Nielsen, Eun Sook Park, Mark Buckup, Vladimir Roudko, Luisanna Pia, Robert Sweeney, Jessica Le Berichel, C. Matthias Wilk, Anela Bektesevic, Brian H. Lee, Nina Bhardwaj, Adeeb H. Rahman, Alessia Baccarini, Sacha Gnjatic, Dana Pe’er, Miriam Merad, Brian D. Brown
Issue&Volume: 2022-03-14
Abstract: While CRISPR screens are helping uncover genes regulating many cell-intrinsic processes,existing approaches are suboptimal for identifying extracellular gene functions, particularlyin the tissue context. Here, we developed an approach for spatial functional genomicscalled Perturb-map. We applied Perturb-map to knock out dozens of genes in parallelin a mouse model of lung cancer and simultaneously assessed how each knockout influencedtumor growth, histopathology, and immune composition. Moreover, we paired Perturb-mapand spatial transcriptomics for unbiased analysis of CRISPR-edited tumors. We foundthat in Tgfbr2 knockout tumors, the tumor microenvironment (TME) was converted toa fibro-mucinous state, and T cells excluded, concomitant with upregulated TGFβ andTGFβ-mediated fibroblast activation, indicating that TGFβ-receptor loss on cancercells increased TGFβ bioavailability and its immunosuppressive effects on the TME.These studies establish Perturb-map for functional genomics within the tissue at single-cellresolution with spatial architecture preserved and provide insight into how TGFβ responsivenessof cancer cells can affect the TME.
DOI: 10.1016/j.cell.2022.02.015
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00195-7