In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolution.

ABSTRACT: The tumour evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues^1-3, the mechanisms that result in only a small number of clones transforming into malignant tumours remain unknown. Here we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes. We couple ultrasound-guided in utero lentiviral microinjections, single-cell RNA sequencing and guide capture to longitudinally monitor clonal expansions and document their underlying gene programmes at single-cell transcriptomic resolution.

SUBMITTER: Renz PF 

PROVIDER: S-EPMC11306103 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature