Chen, H.J. et al. Nat. Biotechnol. 34, 845–851 (2016).

Tissue models are needed to study human cancer progression. To generate a realistic model of the colon, Chen et al. decellularized healthy human colon tissue with detergent and seeded the remaining extracellular matrix scaffold with primary colonic epithelial cells, endothelial cells and myofibroblasts. The native matrix provided a physiological ex vivo model containing intact wild-type mucosa and muscularis mucosa layers as well as vasculature. Seeding with cells carrying mutations in APC and KRAS caused noninvasive tumors to form, and led to submucosal invasion in a background of reduced TGF-β signaling. The system allowed the authors to carry out a transposon-based mutagenesis screen for functional driver mutations leading to colorectal cancer.